THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Introduction and Other Protein Targets

Abstract

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (http://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14747. In addition to this overview, in which are identified Other protein targets which fall outside of the subsequent categorisation, there are six areas of focus: G protein‐coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

1.

Table of contents

S1 Introduction and Other Protein Targets

• S6 Adiponectin receptors

• S7 Blood coagulation components

• S8 Non‐enzymatic BRD containing proteins

• S9 Carrier proteins

• S9 CD molecules

• S11 Methyllysine reader proteins

• S11 Fatty acid‐binding proteins

• S14 Notch receptors

• S15 Regulators of G protein Signaling (RGS) proteins

• S18 Sigma receptors

• S19 Tubulins

S21 G protein‐coupled receptors

• S23 Orphan and other 7TM receptors

• S24 Class A Orphans

• S26 Class C Orphans

• S33 Taste 1 receptors

• S34 Taste 2 receptors

• S35 Other 7TM proteins

• S36 5‐Hydroxytryptamine receptors

• S39 Acetylcholine receptors (muscarinic)

• S41 Adenosine receptors

• S42 Adhesion Class GPCRs

• S45 Adrenoceptors

• S48 Angiotensin receptors

• S50 Apelin receptor

• S51 Bile acid receptor

• S51 Bombesin receptors

• S53 Bradykinin receptors

• S54 Calcitonin receptors

• S56 Calcium‐sensing receptor

• S57 Cannabinoid receptors

• S58 Chemerin receptors

• S59 Chemokine receptors

• S63 Cholecystokinin receptors

• S64 Class Frizzled GPCRs

• S67 Complement peptide receptors

• S68 Corticotropin‐releasing factor receptors

• S69 Dopamine receptors

• S71 Endothelin receptors

• S72 G protein‐coupled estrogen receptor

• S73 Formylpeptide receptors

• S74 Free fatty acid receptors

• S76 GABA_B receptors

• S78 Galanin receptors

• S79 Ghrelin receptor

• S80 Glucagon receptor family

• S81 Glycoprotein hormone receptors

• S82 Gonadotrophin‐releasing hormone receptors

• S83 GPR18, GPR55 and GPR119

• S84 Histamine receptors

• S86 Hydroxycarboxylic acid receptors

• S87 Kisspeptin receptor

• S88 Leukotriene receptors

• S89 Lysophospholipid (LPA) receptors

• S90 Lysophospholipid (S1P) receptors

• S92 Melanin‐concentrating hormone receptors

• S93 Melanocortin receptors

• S94 Melatonin receptors

• S95 Metabotropic glutamate receptors

• S97 Motilin receptor

• S98 Neuromedin U receptors

• S99 Neuropeptide FF/neuropeptide AF receptors

• S100 Neuropeptide S receptor

• S101 Neuropeptide W/neuropeptide B receptors

• S102 Neuropeptide Y receptors

• S103 Neurotensin receptors

• S104 Opioid receptors

• S106 Orexin receptors

• S107 Oxoglutarate receptor

• S108 P2Y receptors

• S110 Parathyroid hormone receptors

• S111 Platelet‐activating factor receptor

• S112 Prokineticin receptors

• S113 Prolactin‐releasing peptide receptor

• S114 Prostanoid receptors

• S116 Proteinase‐activated receptors

• S117 QRFP receptor

• S118 Relaxin family peptide receptors

• S120 Somatostatin receptors

• S121 Succinate receptor

• S122 Tachykinin receptors

• S123 Thyrotropin‐releasing hormone receptors

• S124 Trace amine receptor

• S125 Urotensin receptor

• S126 Vasopressin and oxytocin receptors

• S127 VIP and PACAP receptors

S142 Ion channels

• S143 Ligand‐gated ion channels

• S144 5‐HT₃ receptors

• S146 Acid‐sensing (proton‐gated) ion channels (ASICs)

• S148 Epithelial sodium channel (ENaC)

• S149 GABA_A receptors

• S155 Glycine receptors

• S158 Ionotropic glutamate receptors

• S164 IP₃ receptor

• S165 Nicotinic acetylcholine receptors

• S168 P2X receptors

• S170 ZAC

• S171 Voltage‐gated ion channels

• S171 CatSper and Two‐Pore channels

• S173 Cyclic nucleotide‐regulated channels

• S175 Potassium channels

• S175 Calcium‐ and sodium‐activated potassium channels

• S178 Inwardly rectifying potassium channels

• S182 Two P domain potassium channels

• S185 Voltage‐gated potassium channels

• S189 Ryanodine receptors

• S190 Transient Receptor Potential channels

• S204 Voltage‐gated calcium channels

• S207 Voltage‐gated proton channel

• S208 Voltage‐gated sodium channels

• S210 Other ion channels

• S210 Aquaporins

• S212 Chloride channels

• S213 ClC family

• S215 CFTR

• S216 Calcium activated chloride channel

• S217 Maxi chloride channel

• S218 Volume regulated chloride channels

• S219 Connexins and Pannexins

• S221 Piezo channels

• S222 Sodium leak channel, non‐selective

S229 Nuclear hormone receptors

• S230 1A. Thyroid hormone receptors

• S231 1B. Retinoic acid receptors

• S232 1C. Peroxisome proliferator‐activated receptors

• S233 1D. Rev‐Erb receptors

• S234 1F. Retinoic acid‐related orphans

• S234 1H. Liver X receptor‐like receptors

• S235 1I. Vitamin D receptor‐like receptors

• S236 2A. Hepatocyte nuclear factor‐4 receptors

• S237 2B. Retinoid X receptors

• S238 2C. Testicular receptors

• S238 2E. Tailless‐like receptors

• S239 2F. COUP‐TF‐like receptors

• S239 3B. Estrogen‐related receptors

• S240 4A. Nerve growth factor IB‐like receptors

• S241 5A. Fushi tarazu F1‐like receptors

• S241 6A. Germ cell nuclear factor receptors

• S242 0B. DAX‐like receptors

• S242 Steroid hormone receptors

• S243 3A. Estrogen receptors

• S244 3C. 3‐Ketosteroid receptors

S247 Catalytic receptors

• S248 Cytokine receptor family

• S249 IL‐2 receptor family

• S251 IL‐3 receptor family

• S252 IL‐6 receptor family

• S254 IL‐12 receptor family

• S255 Prolactin receptor family

• S256 Interferon receptor family

• S257 IL‐10 receptor family

• S258 Immunoglobulin‐like family of IL‐1 receptors

• S259 IL‐17 receptor family

• S259 GDNF receptor family

• S260 Integrins

• S264 Pattern recognition receptors

• S264 Toll‐like receptor family

• S266 NOD‐like receptor family

• S268 RIG‐I‐like receptor family

• S269 Receptor Guanylyl Cyclase (RGC) family

• S269 Transmembrane quanylyl cyclases

• S270 Nitric oxide (NO)‐sensitive (soluble) guanylyl cyclase

• S271 Receptor tyrosine kinases (RTKs)

• S272 Type I RTKs: ErbB (epidermal growth factor) receptor family

• S273 Type II RTKs: Insulin receptor family

• S274 Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family

• S275 Type IV RTKs: VEGF (vascular endothelial growth factor) receptor family

• S275 Type V RTKs: FGF (broblast growth factor) receptor family

• S276 Type VI RTKs: PTK7/CCK4

• S277 Type VII RTKs: Neurotrophin receptor/Trk family

• S278 Type VIII RTKs: ROR family

• S278 Type IX RTKs: MuSK

• S279 Type X RTKs: HGF (hepatocyte growth factor) receptor family

• S279 Type XI RTKs: TAM (TYRO3‐, AXL‐ and MER‐TK) receptor family

• S280 Type XII RTKs: TIE family of angiopoietin receptors

• S280 Type XIII RTKs: Ephrin receptor family

• S281 Type XIV RTKs: RET

• S282 Type XV RTKs: RYK

• S282 Type XVI RTKs: DDR (collagen receptor) family

• S283 Type XVII RTKs: ROS receptors

• S283 Type XVIII RTKs: LMR family

• S284 Type XIX RTKs: Leukocyte tyrosine kinase (LTK) receptor family

• S284 Type XX RTKs: STYK1

• S286 Receptor serine/threonine kinase (RSTK) family

• S286 Type I receptor serine/threonine kinases

• S287 Type II receptor serine/threonine kinases

• S287 Type III receptor serine/threonine kinases

• S287 RSTK functional heteromers

• S289 Receptor tyrosine phosphatase (RTP) family

• S291 Tumour necrosis factor (TNF) receptor family

S297 Enzymes

• S301 Acetylcholine turnover

• S302 Adenosine turnover

• S303 Amino acid hydroxylases

• S304 L‐Arginine turnover

• S304 2.1.1.‐ Protein arginine N‐methyltransferases

• S305 Arginase

• S305 Arginine:glycine amidinotransferase

• S305 Dimethylarginine dimethylaminohydrolases

• S306 Nitric oxide synthases

• S307 Carbonic anhydrases

• S308 Carboxylases and decarboxylases

• S308 Carboxylases

• S309 Decarboxylases

• S311 Catecholamine turnover

• S313 Ceramide turnover

• S313 Serine palmitoyltransferase

• S314 Ceramide synthase

• S314 Sphingolipid Δ⁴‐desaturase

• S315 Sphingomyelin synthase

• S315 Sphingomyelin phosphodiesterase

• S316 Neutral sphingomyelinase coupling factors

• S316 Ceramide glucosyltransferase

• S316 Acid ceramidase

• S317 Neutral ceramidases

• S317 Alkaline ceramidases

• S318 Ceramide kinase

• S319 Chromatin modifying enzymes

• S319 2.1.1.‐ Protein arginine N‐methyltransferases

• S320 3.5.1.‐ Histone deacetylases (HDACs)

• S321 Cyclic nucleotide turnover/signalling

• S321 Adenylyl cyclases (ACs)

• S323 Exchange protein activated by cyclic AMP (EPACs)

• S323 Phosphodiesterases, 3’,5’‐cyclic nucleotide (PDEs)

• S327 Cytochrome P450

• S327 CYP2 family

• S328 CYP2 family

• S329 CYP3 family

• S330 CYP4 family

• S331 CYP5, CYP7 and CYP8 families

• S332 CYP11, CYP17, CYP19, CYP20 and CYP21 families

• S333 CYP24, CYP26 and CYP27 families

• S333 CYP39, CYP46 and CYP51 families

• S334 DNA topoisomerases

• S335 Endocannabinoid turnover

• S336 N‐Acylethanolamine turnover

• S337 2‐Acylglycerol ester turnover

• S338 Eicosanoid turnover

• S338 Cyclooxygenase

• S339 Prostaglandin synthases

• S341 Lipoxygenases

• S342 Leukotriene and lipoxin metabolism

• S343 GABA turnover

• S344 Glycerophospholipid turnover

• S345 Phosphoinositide‐specific phospholipase C

• S346 Phospholipase A₂

• S348 Phosphatidylcholine‐specific phospholipase D

• S349 Lipid phosphate phosphatases

• S349 Phosphatidylinositol kinases

• S350 1‐phosphatidylinositol 4‐kinase family

• S351 Phosphatidylinositol‐4‐phosphate 3‐kinase family

• S351 Phosphatidylinositol 3‐kinase family

• S351 Phosphatidylinositol‐4,5‐bisphosphate 3‐kinase family

• S352 1‐phosphatidylinositol‐3‐phosphate 5‐kinase family

• S353 Type I PIP kinases (1‐phosphatidylinositol‐4‐phosphate 5‐kinase family)

• S353 Type II PIP kinases (1‐phosphatidylinositol‐5‐phosphate 4‐kinase family)

• S356 Phosphatidylinositol phosphate kinases

• S356 Haem oxygenase

• S358 Hydrogen sulphide synthesis

• S358 Hydrolases

• S360 Inositol phosphate turnover

• S360 Inositol 1,4,5‐trisphosphate 3‐kinases

• S360 Inositol polyphosphate phosphatases

• S361 Inositol monophosphatase

• S361 Kinases (EC 2.7.x.x)

• S362 Rho kinase

• S362 Protein kinase C (PKC) family

• S363 Alpha subfamily

• S363 Delta subfamily

• S364 Eta subfamily

• S364 FRAP subfamily

• S365 Cyclin‐dependent kinase (CDK) family

• S365 CDK4 subfamily

• S366 GSK subfamily

• S367 Polo‐like kinase (PLK) family

• S367 STE7 family

• S368 Abl family

• S368 Ack family

• S369 Janus kinase (JakA) family

• S369 Src family

• S370 Tec family

• S371 RAF family

• S372 Lanosterol biosynthesis pathway

• S374 Nucleoside synthesis and metabolism

• S376 Paraoxonase (PON) family

• S377 Peptidases and proteinases

• S377 A1: Pepsin

• S377 A22: Presenilin

• S378 C14: Caspase

• S378 M1: Aminopeptidase N

• S379 M2: Angiotensin‐converting (ACE and ACE2)

• S379 M10: Matrix metallopeptidase

• S380 M12: Astacin/Adamalysin

• S380 M28: Aminopeptidase Y

• S381 M19: Membrane dipeptidase

• S381 S1: Chymotrypsin

• S382 T1: Proteasome

• S382 S8: Subtilisin

• S383 S9: Prolyl oligopeptidase

• S383 Poly ADP‐ribose polymerases

• S384 Prolyl hydroxylases

• S384 Sphingosine 1‐phosphate turnover

• S385 Sphingosine kinase

• S386 Sphingosine 1‐phosphate phosphatase

• S387 Sphingosine 1‐phosphate lyase

• S387 Thyroid hormone turnover

• S388 1.14.13.9 Kynurenine 3‐monooxygenase

• S389 2.5.1.58 Protein farnesyltransferase

• S390 3.5.1.‐ Histone deacetylases (HDACs)

• S391 3.5.3.15 Peptidyl arginine deiminases (PADI)

• S391 3.6.5.2 Small monomeric GTPases

• S391 RAS subfamily

• S392 RAB subfamily

S397 Transporters

• S399 ATP‐binding cassette transporter family

• S399 ABCA subfamily

• S401 ABCB subfamily

• S403 ABCC subfamily

• S404 ABCD subfamily of peroxisomal ABC transporters

• S405 ABCG subfamily

• S406 F‐type and V‐type ATPases

• S406 F‐type ATPase

• S407 V‐type ATPase

• S407 P‐type ATPases

• S407 Na⁺/K⁺‐ATPases

• S408 Ca²⁺‐ATPases

• S408 H⁺/K⁺‐ATPases

• S408 Cu⁺‐ATPases

• S409 Phospholipid‐transporting ATPases

• S409 SLC superfamily of solute carriers

• S410 SLC1 family of amino acid transporters

• S410 Glutamate transporter subfamily

• S412 Alanine/serine/cysteine transporter subfamily

• S413 SLC2 family of hexose and sugar alcohol transporters

• S413 Class I transporters

• S414 Class II transporters

• S415 Proton‐coupled inositol transporter

• S415 SLC3 and SLC7 families of heteromeric amino acid transporters (HATs)

• S415 SLC3 family

• S416 SLC7 family

• S417 SLC4 family of bicarbonate transporters

• S417 Anion exchangers

• S418 Sodium‐dependent HCO₃ ⁻ transporters

• S418 SLC5 family of sodium‐dependent glucose transporters

• S419 Hexose transporter family

• S420 Choline transporter

• S421 Sodium iodide symporter, sodium‐dependent multivitamin transporter and sodium‐coupled monocarboxylate transporters

• S422 Sodium myo‐inositol cotransporter transporters

• S423 SLC6 neurotransmitter transporter family

• S423 Monoamine transporter subfamily

• S424 GABA transporter subfamily

• S425 Glycine transporter subfamily

• S427 Neutral amino acid transporter subfamily

• S428 SLC8 family of sodium/calcium exchangers

• S429 SLC9 family of sodium/hydrogen exchangers

• S429 SLC10 family of sodium‐bile acid co‐transporters

• S431 SLC11 family of proton‐coupled metal ion transporters

• S431 SLC12 family of cation‐coupled chloride transporters

• S433 SLC13 family of sodium‐dependent sulphate/carboxylate transporters

• S434 SLC14 family of facilitative urea transporters

• S435 SLC15 family of peptide transporters

• S437 SLC16 family of monocarboxylate transporters

• S438 SLC17 phosphate and organic anion transporter family

• S438 Type I sodium‐phosphate co‐transporters

• S439 Sialic acid transporter

• S439 Vesicular glutamate transporters (VGLUTs)

• S440 Vesicular nucleotide transporter

• S440 SLC18 family of vesicular amine transporters

• S442 SLC19 family of vitamin transporters

• S443 SLC20 family of sodium‐dependent phosphate transporters

• S443 SLC22 family of organic cation and anion transporters

• S444 Organic cation transporters (OCT)

• S445 Organic zwitterions/cation transporters (OCTN)

• S446 Organic anion transporters (OATs)

• S446 Urate transporter

• S447 Atypical SLC22B subfamily

• S448 SLC23 family of ascorbic acid transporters

• S449 SLC24 family of sodium/potassium/calcium exchangers

• S450 SLC25 family of mitochondrial transporters

• S450 Mitochondrial di‐ and tri‐carboxylic acid transporter subfamily

• S451 Mitochondrial amino acid transporter subfamily

• S452 Mitochondrial phosphate transporters

• S452 Mitochondrial nucleotide transporter subfamily

• S453 Mitochondrial uncoupling proteins

• S454 Miscellaneous SLC25 mitochondrial transporters

• S454 SLC26 family of anion exchangers

• S454 Selective sulphate transporters

• S455 Chloride/bicarbonate exchangers

• S455 Anion channels

• S456 Other SLC26 anion exchangers

• S457 SLC27 family of fatty acid transporters

• S458 SLC28 and SLC29 families of nucleoside transporters

• S458 SLC28 family

• S459 SLC29 family

• S461 SLC30 zinc transporter family

• S461 SLC31 family of copper transporters

• S462 SLC32 vesicular inhibitory amino acid transporter

• S463 SLC33 acetylCoA transporter

• S464 SLC34 family of sodium phosphate co‐transporters

• S465 SLC35 family of nucleotide sugar transporters

• S466 SLC36 family of proton‐coupled amino acid transporters

• S468 SLC37 family of phosphosugar/phosphate exchangers

• S468 SLC38 family of sodium‐dependent neutral amino acid transporters

• S469 System A‐like transporters

• S469 System N‐like transporters

• S470 Orphan SLC38 transporters

• S470 SLC39 family of metal ion transporters

• S471 SLC40 iron transporter

• S472 SLC41 family of divalent cation transporters

• S473 SLC42 family of Rhesus glycoprotein ammoniumtransporters

• S473 SLC43 family of large neutral amino acid transporters

• S474 SLC44 choline transporter‐like family

• S475 SLC45 family of putative sugar transporters

• S475 SLC46 family of folate transporters

• S477 SLC47 family of multidrug and toxin extrusion transporters

• S477 SLC48 heme transporter

• S478 SLC49 family of FLVCR‐related heme transporters

• S479 SLC50 sugar transporter

• S479 SLC51 family of steroid‐derived molecule transporters

• S480 SLC52 family of riboflavin transporters

• S481 SLC53 Phosphate carriers

• S481 SLC54 Mitochondrial pyruvate carriers

• S482 SLC55 Mitochondrial cation/proton exchangers

• S482 SLC56 Sideroflexins

• S483 SLC57 NiPA‐like magnesium transporter family

• S483 SLC58 MagT‐like magnesium transporter family

• S484 SLC59 Sodium‐dependent lysophosphatidylcholine symporter family

• S484 SLC60 Glucose transporters

• S485 SLC61 Molybdate transporter family

• S485 SLC62 Pyrophosphate transporters

• S486 SLC63 Sphingosine phosphate transporters

• S486 SLC64 Golgi Ca2+/H+ exchangers

• S487 SLC65 NPC‐type cholesterol transporters

• S488 SLCO family of organic anion transporting polypeptides

Introduction

In order to allow clarity and consistency in pharmacology, there is a need for a comprehensive organisation and presentation of the targets of drugs. This is the philosophy of the IUPHAR/BPS Guide to PHARMACOLOGY presented on the online free access database (https://www.guidetopharmacology.org/). This database is supported by the British Pharmacological Society (BPS), the International Union of Basic and Clinical Pharmacology (IUPHAR), the University of Edinburgh and previously the Wellcome Trust. Data included in the Guide to PHARMACOLOGY are derived in large part from interactions with the subcommittees of the Nomenclature Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR). A major influence on the development of the database was Tony Harmar (1951‐2014), who worked with a passion to establish the curators as a team of highly informed and informative individuals, with a focus on high‐quality data input, ensuring a suitably validated dataset. The Editors of the Concise Guide have compiled the individual records, in concert with the team of Curators, drawing on the expert knowledge of these latter subcommittees. The tables allow an indication of the status of the nomenclature for the group of targets listed, usually previously published in Pharmacological Reviews. In the absence of an established subcommittee, advice from several prominent, independent experts has generally been obtained to produce an authoritative consensus on nomenclature, which attempts to fit in within the general guidelines from NC‐IUPHAR. This current edition, the Concise Guide to PHARMACOLOGY 2019/20, is the latest snapshot of the database in print form, following on from the Concise Guide to PHARMACOLOGY 2017/18. It contains data drawn from the online database as a rapid overview of the major pharmacological targets. Thus, there are many fewer targets presented in the Concise Guide compared to the online database. The priority for inclusion in the Concise Guide is the presence of quantitative pharmacological data for human proteins. This means that often orphan family members are not presented in the Concise Guide, although structural information is available on the online database. The organisation of the data is tabular (where appropriate) with a standardised format, where possible on a single page, intended to aid understanding of, and comparison within, a particular target group. The Concise Guide is intended as an initial resource, with links to additional reviews and resources for greater depth and information. Pharmacological and structural data focus primarily on human gene products, wherever possible, with links to HGNC gene nomenclature and UniProt IDs. In a few cases, where data from human proteins are limited, data from other species are indicated. Pharmacological tools listed are prioritised on the basis of selectivity and availability. That is, agents (agonists, antagonists, inhibitors, activators, etc.) are included where they are both available (by donation or from commercial sources, now or in the near future) AND the most selective. The Concise Guide is divided into seven sections, which comprise pharmacological targets of similar structure/function. These are G protein‐coupled receptors, ion channels (combining previous records of ligand‐gated, voltage‐gated and other ion channels), catalytic receptors, nuclear hormone receptors, enzymes, transporters and other protein targets. We hope that the Concise Guide will provide for researchers, teachers and students a state‐of‐the art source of accurate, curated information on the background to their work that they will use in the Introductions to their Research Papers or Reviews, or in supporting their teaching and studies. We recommend that any citations to information in the Concise Guide are presented in the following format: Alexander SPH et al. (2019). The Concise Guide to PHARMACOLOGY 2019/20: Introduction and Other Protein Targets. Br J Pharmacol 176: S1–S20. In this overview are listed protein targets of pharmacological interest, which are not G protein‐coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, transporters or enzymes.

Acknowledgements

We are extremely grateful to the British Pharmacological Society and the International Union of Basic and Clinical Pharmacology, for financial support of the website and for advice from the NC‐IUPHAR subcommittees. We thank the University of Edinburgh, who host the http://www.guidetopharmacology.org website. Previously, the International Union of Basic and Clinical Pharmacology and the Wellcome Trust (099156/Z/12/Z]) also supported the initiation and expansion of the database. We are also tremendously grateful to the long list of collaborators from NC‐IUPHAR subcommittees and beyond, who have assisted in the construction of the Concise Guide to PHARMACOLOGY 2019/20 and the online database http://www.guidetopharmacology.org.

Conflict of interest

The authors state that there are no conflicts of interest to disclose.

Family structure

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1021

S6 Adiponectin receptors

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=982

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=970

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=983

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=971

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=910

S7 Blood coagulation components

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=866

S8 Non‐enzymatic BRD containing proteins

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=966

S8 Carrier proteins

S9 CD molecules

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=997

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=998

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=986

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=901

S11 Methyllysine reader proteins

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=916

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=930

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=915

S11 Fatty acid-binding proteins

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=946

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=935

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=784

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=954

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=949

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=985

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=987

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=984

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=868

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=889

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=876

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=888

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=934

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=924

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=919

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=921

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=991

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=941

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=942

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=945

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=929

S14 Notch receptors

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1001

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=906

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=907

S15 Regulators of G protein Signaling (RGS) proteins

S15 RZ family

S15 R4 family

S16 R7 family

S17 R12 family

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=932

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=905

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=875

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1000

S18 Sigma receptors

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=989

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=972

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=1019

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=973

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=974

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=990

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=995

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=996

S19 Tubulins

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=904

– http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=903

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=106

Overview

Adiponectin receptors (provisional nomenclature, http://www.ensembl.org/Homo_sapiens/Gene/Family/Genes?family=ENSFM00500000270960) respond to the 30 kDa complement‐related protein hormone adiponectin (also known as https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13633: adipocyte, C1q and collagen domain‐containing protein; ACRP30, adipose most abundant gene transcript 1; apM‐1; gelatin‐binding protein: http://www.uniprot.org/uniprot/Q15848) originally cloned from adipocytes [http://www.ncbi.nlm.nih.gov/pubmed/8619847?dopt=AbstractPlus]. Although sequence data suggest 7TM domains, immunological evidence indicates that, contrary to typical 7TM topology, the carboxyl terminus is extracellular, while the amino terminus is intracellular [http://www.ncbi.nlm.nih.gov/pubmed/12802337?dopt=AbstractPlus]. Signalling through these receptors appears to avoid G proteins; modelling based on the crystal structures of the adiponectin receptors suggested ceramidase acivity, which would make these the first in a new family of catalytic receptors [http://www.ncbi.nlm.nih.gov/pubmed/25855295?dopt=AbstractPlus].

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=649	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=650
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:24040, http://www.uniprot.org/uniprot/Q96A54	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:24041, http://www.uniprot.org/uniprot/Q86V24
Rank order of potency	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3727 (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13633, http://www.uniprot.org/uniprot/Q15848) > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3726 (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13633, http://www.uniprot.org/uniprot/Q15848)	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3727 (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13633, http://www.uniprot.org/uniprot/Q15848) = http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3726 (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13633, http://www.uniprot.org/uniprot/Q15848)

Comments

T‐Cadherin (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1753, http://www.uniprot.org/uniprot/P55290) has also been suggested to be a receptor for (hexameric) adiponectin [http://www.ncbi.nlm.nih.gov/pubmed/15210937?dopt=AbstractPlus].

Further reading on Adiponectin receptors

Fisman EZ et al. (2014) Adiponectin: a manifold therapeutic target for metabolic syndrome, diabetes, and coronary disease? Cardiovasc Diabetol 13: 103 [https://www.ncbi.nlm.nih.gov/pubmed/24957699?dopt=AbstractPlus]

Okada‐Iwabu M et al. (2018) Structure and function analysis of adiponectin receptors toward development of novel antidiabetic agents promoting healthy longevity. Endocr J 65: 971‐977 [https://www.ncbi.nlm.nih.gov/pubmed/30282888]

Ruan H et al. (2016) Adiponectin signaling and function in insulin target tissues. J Mol Cell Biol 8: 101‐9 [https://www.ncbi.nlm.nih.gov/pubmed/26993044?dopt=AbstractPlus]

Wang Y et al. (2017) Cardiovascular Adiponectin Resistance: The Critical Role of Adiponectin Receptor Modification. Trends Endocrinol. Metab. 28: 519‐530 [https://www.ncbi.nlm.nih.gov/pubmed/28473178?dopt=AbstractPlus]

Zhao L et al. (2014) Adiponectin and insulin cross talk: the microvascular connection. Trends Cardiovasc. Med. 24: 319‐24 [https://www.ncbi.nlm.nih.gov/pubmed/25220977?dopt=AbstractPlus]

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=853

Overview

Coagulation as a process is interpreted as a mechanism for reducing excessive blood loss through the generation of a gel‐like clot local to the site of injury. The process involves the activation, adhesion (see http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=760), degranulation and aggregation of platelets, as well as proteins circulating in the plasma. The coagulation cascade involves multiple proteins being converted to more active forms from less active precursors, typically through proteolysis (see http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=759&familyType=ENZYME). Listed here are the components of the coagulation cascade targetted by agents in current clinical usage.

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2606	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2607	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2632
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3542, http://www.uniprot.org/uniprot/P12259	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3546, http://www.uniprot.org/uniprot/P00451	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:775, http://www.uniprot.org/uniprot/P01008
Selective activators	–	–	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4214 (pK d 7.8) [http://www.ncbi.nlm.nih.gov/pubmed/23598032?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6819 (pK d 7.5) [http://www.ncbi.nlm.nih.gov/pubmed/12383040?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6803 [http://www.ncbi.nlm.nih.gov/pubmed/3744129?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6804 [http://www.ncbi.nlm.nih.gov/pubmed/8137606?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/19398784?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6811 [http://www.ncbi.nlm.nih.gov/pubmed/7667822?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6846 [http://www.ncbi.nlm.nih.gov/pubmed/7528134?dopt=AbstractPlus]
Selective inhibitors	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6788 (Antithrombotic effect thought to occur via inhibition of factors Va and VIIIa) [http://www.ncbi.nlm.nih.gov/pubmed/11714212?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/11463021?dopt=AbstractPlus]	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6788 (Antithrombotic effect thought to occur via inhibition of factors Va and VIIIa) [http://www.ncbi.nlm.nih.gov/pubmed/11714212?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/11463021?dopt=AbstractPlus]	–

Further reading on Blood coagulation components

Astermark J. (2015) FVIII inhibitors: pathogenesis and avoidance. Blood 125: 2045‐51 [https://www.ncbi.nlm.nih.gov/pubmed/25712994?dopt=AbstractPlus]

Girolami A et al. (2017) New clotting disorders that cast new light on blood coagulation and may play a role in clinical practice. J. Thromb. Thrombolysis 44: 71‐75 [https://www.ncbi.nlm.nih.gov/pubmed/28251495?dopt=AbstractPlus]

Rana K et al. (2016) Blood flow and mass transfer regulation of coagulation. Blood Rev. 30: 357‐68 [https://www.ncbi.nlm.nih.gov/pubmed/27133256?dopt=AbstractPlus]

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=867

Overview

Bromodomains bind proteins with acetylated lysine residues, such as histones, to regulate gene transcription. Listed herein are examples of bromodomain‐containing proteins for which sufficient pharmacology exists.

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2721	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2722	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2734	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2738	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2740
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:962, http://www.uniprot.org/uniprot/Q9UIF9	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:963, http://www.uniprot.org/uniprot/Q9UIF8	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2348, http://www.uniprot.org/uniprot/Q92793	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:30064, http://www.uniprot.org/uniprot/Q86U86	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11100, http://www.uniprot.org/uniprot/P51532
Selective inhibitors	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8233 (pK d 6.6) [85]	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8233 (Binding) (pK d 6.9) [85]	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8236 (pK d 6.8) [84]	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7915 (Binding) (pK d 7.3) [95]	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7915 (Binding) (pK d 7.1) [95]

Further reading on Non‐enzymatic BRD containing proteins

Fujisawa T et al. (2017) Functions of bromodomain‐containing proteins and their roles in homeostasis and cancer. Nat. Rev. Mol. Cell Biol. 18: 246‐262 [https://www.ncbi.nlm.nih.gov/pubmed/28053347?dopt=AbstractPlus]

Myrianthopoulos V & Mikros E. (2019) From bench to bedside, via desktop. Recent advances in the application of cutting‐edge in silico tools in the research of drugs targeting bromodomain modules. Biochem Pharmacol 159: 40‐51 [https://www.ncbi.nlm.nih.gov/pubmed/30414936]

Nicholas DA et al. (2017) BET bromodomain proteins and epigenetic regulation of inflammation: implications for type 2 diabetes and breast cancer. Cell. Mol. Life Sci. 74: 231‐243 [https://www.ncbi.nlm.nih.gov/pubmed/27491296?dopt=AbstractPlus]

Ramadoss M & Mahadevan V. (2018) Targeting the cancer epigenome: synergistic therapy with bromodomain inhibitors. Drug Discov Today 23: 76‐89 [https://www.ncbi.nlm.nih.gov/pubmed/28943305]

Yang CY et al. (2019) Small‐molecule PROTAC degraders of the Bromodomain and Extra Terminal (BET) proteins ‐ A review. Drug Discov Today Technol 31: 43‐51 [https://www.ncbi.nlm.nih.gov/pubmed/31200858]

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=911

Overview

Transthyretin (TTR) is a homo‐tetrameric protein which transports thyroxine in the plasma and cerebrospinal fluid and retinol (vitamin A) in the plasma. Many disease causing mutations in the protein have been reported, many of which cause complex dissociation and protein mis‐assembly and deposition of toxic aggregates amyloid fibril formation [http://www.ncbi.nlm.nih.gov/pubmed/23716704?dopt=AbstractPlus]. These amyloidogenic mutants are linked to the development of pathological amyloidoses, including familial amyloid polyneuropathy (FAP) [http://www.ncbi.nlm.nih.gov/pubmed/12978172?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/8894411?dopt=AbstractPlus], familial amyloid cardiomyopathy (FAC) [http://www.ncbi.nlm.nih.gov/pubmed/9017939?dopt=AbstractPlus], amyloidotic vitreous opacities, carpal tunnel syndrome [http://www.ncbi.nlm.nih.gov/pubmed/10403814?dopt=AbstractPlus] and others. In old age, non‐mutated TTR can also form pathological amyloid fibrils [http://www.ncbi.nlm.nih.gov/pubmed/7016817?dopt=AbstractPlus]. Pharmacological intervention to reduce or prevent TTR dissociation is being pursued as a theapeutic strategy. To date one small molecule kinetic stabilising molecule (http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8378) has been approved for FAP, and is being evaluated in clinical trials for other TTR amyloidoses.

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2851
Common abbreviation	TTR
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12405, http://www.uniprot.org/uniprot/P02766

Further reading on Carrier proteins

Adams D et al. (2019) Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease. Nat Rev Neurol 15: 387‐404 [https://www.ncbi.nlm.nih.gov/pubmed/31209302]

Dellière S et al. (2017) Is transthyretin a good marker of nutritional status? Clin Nutr 36: 364‐370 [https://www.ncbi.nlm.nih.gov/pubmed/27381508?dopt=AbstractPlus]

Galant NJ et al. (2017) Transthyretin amyloidosis: an under‐recognized neuropathy and cardiomyopathy. Clin. Sci. 131: 395‐409 [https://www.ncbi.nlm.nih.gov/pubmed/28213611?dopt=AbstractPlus]

Yokoyama T & Mizuguchi M. (2018) Inhibition of the Amyloidogenesis of Transthyretin by Natural Products and Synthetic Compounds. Biol Pharm Bull 41: 979‐984 [https://www.ncbi.nlm.nih.gov/pubmed/29962408]

Ruberg FL et al. (2019) Transthyretin Amyloid Cardiomyopathy: JACC State‐of‐the‐Art Review. J Am Coll Cardiol 73: 2872‐2891 [https://www.ncbi.nlm.nih.gov/pubmed/31171094]

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=852

Overview

Cluster of differentiation refers to an attempt to catalogue systematically a series of over 300 cell‐surface proteins associated with immunotyping. Many members of the group have identified functions as enzymes (for example, see http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=1232) or receptors (for example, see http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2441). Many CDs are targeted for therapeutic gain using antibodies for the treatment of proliferative disorders. A full listing of all the Clusters of Differentiation proteins is not possible in the Guide to PHARMACOLOGY; listed herein are selected members of the family targeted for therapeutic gain.

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2600	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2742	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2917	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2628)	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2601
Common abbreviation	–	–	–	–	SIGLEC‐3
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1639, http://www.uniprot.org/uniprot/P06729	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1674, http://www.uniprot.org/uniprot/P07766	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1691, http://www.uniprot.org/uniprot/P30203	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7315, http://www.uniprot.org/uniprot/P11836	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1659, http://www.uniprot.org/uniprot/P20138
Selective inhibitors	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6787 [http://www.ncbi.nlm.nih.gov/pubmed/11970990?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/12089534?dopt=AbstractPlus]	–	–	–	–
Antibodies	–	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7385 (Binding) [http://www.ncbi.nlm.nih.gov/pubmed/20190561?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6889 (Binding) [http://www.ncbi.nlm.nih.gov/pubmed/3105134?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8458 (Binding) [http://www.ncbi.nlm.nih.gov/pubmed/8436176?dopt=AbstractPlus]	–	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6778 (Binding) (pK d 9.9) [52], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6780 (Binding) (pK d 8.5) [http://www.ncbi.nlm.nih.gov/pubmed/15102696?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6777 (Binding), http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6941 (Binding) [http://www.ncbi.nlm.nih.gov/pubmed/21378274?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/23537278?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6781 (Binding)	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7983 (Binding) (pK d ∼10) [http://www.ncbi.nlm.nih.gov/pubmed/1458463?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6775 (Binding) [http://www.ncbi.nlm.nih.gov/pubmed/10720144?dopt=AbstractPlus]

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2602	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2744	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2745	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2743)	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2760)	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2918
Common abbreviation	–	–	–	CTLA‐4	PD‐1	–
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1804, http://www.uniprot.org/uniprot/P31358	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1700, http://www.uniprot.org/uniprot/P33681	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1705, http://www.uniprot.org/uniprot/P42081	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2505, http://www.uniprot.org/uniprot/P16410	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:8760, http://www.uniprot.org/uniprot/Q15116	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:19319, http://www.uniprot.org/uniprot/Q9UGN4
Endogenous ligands	–	–	–	–	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=9606 (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:17635, https://www.uniprot.org/uniprot/Q9NZQ7) (Binding)	–
Selective inhibitors	–	abatacept (pK d ∼7.9) [51, 103]	abatacept (pKd ∼7.9) [http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6891], belatacept [44]	–	–	–
Antibodies	alemtuzumab (http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6770, 86]	–	–	ipilimumab (Binding) (http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6888) [30], tremelimumab (Binding) (http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8462]	pembrolizumab (Binding) (pK d http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7499 (Binding) (phttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7499 d 9.1) [http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7335]	–

Comments

The endogenous ligands for human PD‐1 are programmed cell death 1 ligand 1 (PD‐L1 aka http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7693 (https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:17635, http://www.uniprot.org/uniprot/Q9NZQ7)) and programmed cell death 1 ligand 2 (PD‐L2; https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:18731). These ligands are cell surface peptides, normally involved in immune system regulation. Expression of PD‐1 by cancer cells induces immune tolerance and evasion of immune system attack. Anti‐PD‐1 monoclonal antibodies are used to induce immune checkpoint blockade as a therapeutic intervention in cancer, effectively re‐establishing immune vigilance. http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7499 was the first anti‐PD‐1 antibody to be approved by the US FDA.

Further reading on CD molecules

Gabius HJ et al. (2015) The glycobiology of the CD system: a dictionary for translating marker designations into glycan/lectin structure and function. Trends Biochem. Sci. 40: 360‐76 [https://www.ncbi.nlm.nih.gov/pubmed/25981696?dopt=AbstractPlus]

Vosoughi T et al. (2019) CD markers variations in chronic lymphocytic leukemia: New insights into prognosis. J Cell Physiol. 234: 19420‐39 [https://www.ncbi.nlm.nih.gov/pubmed/31049958]

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=902

Overview

Methyllysine reader proteins bind to methylated proteins, such as histones, allowing regulation of gene expression.

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2830
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:23035, http://www.uniprot.org/uniprot/Q96JM7
Selective agonists	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8232 [http://www.ncbi.nlm.nih.gov/pubmed/23292653?dopt=AbstractPlus]

Further reading on Methyllysine reader proteins

Daskalaki MG et al. (2018) Histone methylation and acetylation in macrophages as a mechanism for regulation of inflammatory responses. J Cell Physiol. 233: 6495‐9507 [https://www.ncbi.nlm.nih.gov/pubmed/29574768]

Furuya K et al. (2019) Epigenetic interplays between DNA demethylation and histone methylation for protecting oncogenesis. J Biochem. 165: 297‐299 [https://www.ncbi.nlm.nih.gov/pubmed/30605533]

Levy D. (2019) Lysine methylation signaling of non‐histone proteins in the nucleus. Cell Mol Life Sci 76: 2873‐83 [https://www.ncbi.nlm.nih.gov/pubmed/31123776]

Li J et al. (2019) Understanding histone H3 lysine 36 methylation and its deregulation in disease. Cell Mol Life Sci in press [https://www.ncbi.nlm.nih.gov/pubmed/31147750]

Shafabakhsh R et al. (2019) Role of histone modification and DNA methylation in signaling pathways involved in diabetic retinopathy. J Cell Physiol. 234: 7839‐7846 [https://www.ncbi.nlm.nih.gov/pubmed/30515789]

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=783

Overview

Fatty acid‐binding proteins are low molecular weight (100‐130 aa) chaperones for long chain fatty acids, fatty acyl CoA esters, eicosanoids, retinols, retinoic acids and related metabolites and are usually regarded as being responsible for allowing the otherwise hydrophobic ligands to be mobile in aqueous media. These binding proteins may perform functions extracellularly (e.g. in plasma) or transport these agents; to the nucleus to interact with nuclear receptors (principally PPARs and retinoic acid receptors http://www.ncbi.nlm.nih.gov/pubmed/17882463?dopt=AbstractPlus]) or for interaction with metabolic enzymes. Although sequence homology is limited, crystallographic studies suggest conserved 3D structures across the group of binding proteins.

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2531	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2532	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2533	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2534	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2535
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3555, http://www.uniprot.org/uniprot/P07148	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3556, http://www.uniprot.org/uniprot/P12104	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3557, http://www.uniprot.org/uniprot/P05413	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3559, http://www.uniprot.org/uniprot/P15090	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3560, http://www.uniprot.org/uniprot/Q01469
Rank order of potency	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3377, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1054 > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1055, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1052 > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2391, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1049 [http://www.ncbi.nlm.nih.gov/pubmed/7929039?dopt=AbstractPlus]	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3377 > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1055,http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1054 > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1052 > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2391, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1049 [http://www.ncbi.nlm.nih.gov/pubmed/7929039?dopt=AbstractPlus]	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3377, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1054, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1055 > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1052, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1049, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2391 [http://www.ncbi.nlm.nih.gov/pubmed/7929039?dopt=AbstractPlus]	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1054, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1055, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3377, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1052 > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1049, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2391 [http://www.ncbi.nlm.nih.gov/pubmed/7929039?dopt=AbstractPlus]	–
Inhibitors	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7186 (pK i 7.6) [http://www.ncbi.nlm.nih.gov/pubmed/18533710?dopt=AbstractPlus] – Rat, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2662 (pK i 6.5) [http://www.ncbi.nlm.nih.gov/pubmed/18533710?dopt=AbstractPlus] – Rat, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6736 (pK i 5.1) [http://www.ncbi.nlm.nih.gov/pubmed/19754198?dopt=AbstractPlus] – Mouse	–	–	–	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8797 (pK i 8.7) [http://www.ncbi.nlm.nih.gov/pubmed/17502136?dopt=AbstractPlus]
Selective inhibitors	–	–	–	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8788 (pK i >9) [http://www.ncbi.nlm.nih.gov/pubmed/21481589?dopt=AbstractPlus]	–
Comments	A broader substrate specificity than other FABPs, binding two fatty acids per protein [http://www.ncbi.nlm.nih.gov/pubmed/9054409?dopt=AbstractPlus].	Crystal structure of the rat FABP2 [http://www.ncbi.nlm.nih.gov/pubmed/2671390?dopt=AbstractPlus].	Crystal structure of the human FABP3 [http://www.ncbi.nlm.nih.gov/pubmed/7922029?dopt=AbstractPlus].	–	Crystal structure of the human FABP5 [http://www.ncbi.nlm.nih.gov/pubmed/10493790?dopt=AbstractPlus].

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2536	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2537	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2544	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2538	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2584
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3561, http://www.uniprot.org/uniprot/P51161	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3562, http://www.uniprot.org/uniprot/O15540	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9117, http://www.uniprot.org/uniprot/P02689	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3563, http://www.uniprot.org/uniprot/Q0Z7S8	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:34524, http://www.uniprot.org/uniprot/A6NFH5
Comments	Able to transport bile acids [http://www.ncbi.nlm.nih.gov/pubmed/23603607?dopt=AbstractPlus].	Crystal structure of the human FABP7 [http://www.ncbi.nlm.nih.gov/pubmed/10854433?dopt=AbstractPlus].	In silico modelling suggests that PMP2/FABP8 can bind both fatty acids and cholesterol [http://www.ncbi.nlm.nih.gov/pubmed/20421974?dopt=AbstractPlus].	–	–

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2546	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2547	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2548	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2549	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2550		http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2551
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9919, http://www.uniprot.org/uniprot/P09455	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9920, http://www.uniprot.org/uniprot/P50120	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9921, http://www.uniprot.org/uniprot/P10745	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9922, http://www.uniprot.org/uniprot/P02753	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:15847, http://www.uniprot.org/uniprot/P82980		https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:30316, http://www.uniprot.org/uniprot/Q96R05
Rank order of potency	–	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3377 > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1055, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1054, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1052, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1049, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2391 [http://www.ncbi.nlm.nih.gov/pubmed/10852718?dopt=AbstractPlus]	–	–	–	–
Inhibitors	–	–	–	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8792 (pIC50 7.8) [http://www.ncbi.nlm.nih.gov/pubmed/24835984?dopt=AbstractPlus]	–	–

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2545	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2529	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2530
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10024, http://www.uniprot.org/uniprot/P12271	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2338, http://www.uniprot.org/uniprot/P29762	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:2339, http://www.uniprot.org/uniprot/P29373
Rank order of potency	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6669, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6670 > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6673, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6671, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6672, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2350, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=4053 [http://www.ncbi.nlm.nih.gov/pubmed/9541407?dopt=AbstractPlus]	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2644 > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2645 http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=3377 > http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1055, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1054, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1052, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1049, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2391 [http://www.ncbi.nlm.nih.gov/pubmed/10852718?dopt=AbstractPlus]	–

Comments

Although not tested at all FABPs, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6735 exhibits high affinity for FABP4 (pIC50 8.8) compared to FABP3 or FABP5 (pIC50 <6.6) [http://www.ncbi.nlm.nih.gov/pubmed/17554340?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/17502136?dopt=AbstractPlus]. http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6736 is reported to interfere with FABP4 action [http://www.ncbi.nlm.nih.gov/pubmed/19754198?dopt=AbstractPlus]. Ibuprofen displays some selectivity for FABP4 (pIC₅₀ 5.5) relative to FABP3 (pIC₅₀ 3.5) and FABP5 (pIC₅₀ 3.8) [http://www.ncbi.nlm.nih.gov/pubmed/24248795?dopt=AbstractPlus]. Fenofibric acid displays some selectivity for FABP5 (pIC₅₀ 5.5) relative to FABP3 (pIC₅₀ 4.5) and FABP4 (pIC₅₀ 4.6) [http://www.ncbi.nlm.nih.gov/pubmed/24248795?dopt=AbstractPlus]. Multiple pseudogenes for the FABPs have been identified in the human genome.

Further reading on Fatty acid‐binding proteins

Gajda AM et al. (2015) Enterocyte fatty acid‐binding proteins (FABPs): different functions of liver and intestinal FABPs in the intestine. Prostaglandins Leukot. Essent. Fatty Acids 93: 9‐16 [https://www.ncbi.nlm.nih.gov/pubmed/25458898?dopt=AbstractPlus]

Glatz JF. (2015) Lipids and lipid binding proteins: a perfect match. Prostaglandins Leukot Essent Fatty Acids 93: 45‐9 [https://www.ncbi.nlm.nih.gov/pubmed/25154384?dopt=AbstractPlus]

Hotamisligil GS et al. (2015) Metabolic functions of FABPs–mechanisms and therapeutic implications. Nat Rev Endocrinol 11: 592‐605 [https://www.ncbi.nlm.nih.gov/pubmed/26260145?dopt=AbstractPlus]

Matsumata M et al. (2016) Fatty acid binding proteins and the nervous system: Their impact on mental conditions. Neurosci. Res. 102: 47‐55 [https://www.ncbi.nlm.nih.gov/pubmed/25205626?dopt=AbstractPlus]

Osumi T et al. (2016) Heart lipid droplets and lipid droplet‐binding proteins: Biochemistry, physiology, and pathology. Exp. Cell Res. 340: 198‐204 [https://www.ncbi.nlm.nih.gov/pubmed/26524506?dopt=AbstractPlus]

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=914

Overview

The canonical Notch signalling pathway has four type I transmembrane Notch receptors (Notch1‐4) and five ligands (DLL1, 2 and 3, and Jagged 1‐2). Each member of this highly conserved receptor family plays a unique role in cell‐fate determination during embryogenesis, differentiation, tissue patterning, proliferation and cell death [http://www.ncbi.nlm.nih.gov/pubmed/20971825?dopt=AbstractPlus]. As the Notch ligands are also membrane bound, cells have to be in close proximity for receptorligand interactions to occur. Cleavage of the intracellular domain (ICD) of activated Notch receptors by γ‐secretase is required for downstream signalling and Notch‐induced transcriptional modulation [http://www.ncbi.nlm.nih.gov/pubmed/10206645?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/16530044?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/9620803?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/16530045?dopt=AbstractPlus]. This is why γ‐secretase inhibitors can be used to downregulate Notch signalling and explains their anticancer action. One such small molecule is http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7338 [http://www.ncbi.nlm.nih.gov/pubmed/19773430?dopt=AbstractPlus], although development of this compound has been terminated following an unsuccessful Phase II single agent clinical trial in metastatic colorectal cancer [http://www.ncbi.nlm.nih.gov/pubmed/22445247?dopt=AbstractPlus].

Aberrant Notch signalling is implicated in a number of human cancers [http://www.ncbi.nlm.nih.gov/pubmed/17344417?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/24651013?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/18079963?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/17173050?dopt=AbstractPlus], with http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8451 and http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8453 identified as antibody inhibitors of ligand:receptor binding [http://www.ncbi.nlm.nih.gov/pubmed/25388163?dopt=AbstractPlus].

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2861	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2859	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2860	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2862
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7881, http://www.uniprot.org/uniprot/P46531	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7882, http://www.uniprot.org/uniprot/Q04721	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7883, http://www.uniprot.org/uniprot/Q9UM47	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7884, http://www.uniprot.org/uniprot/Q99466
Comments	Various types of activating and inactivating NOTCH1 mutations have been reported to be associated with human diseases, for example: aortic valve disease [http://www.ncbi.nlm.nih.gov/pubmed/16025100?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/18593716?dopt=AbstractPlus], Adams‐Oliver syndrome 5 [http://www.ncbi.nlm.nih.gov/pubmed/25132448?dopt=AbstractPlus], T‐cell acute lymphoblastic leukemia (T‐ALL) [http://www.ncbi.nlm.nih.gov/pubmed/15472075?dopt=AbstractPlus], chronic lymphocytic leukemia (CLL) [http://www.ncbi.nlm.nih.gov/pubmed/21642962?dopt=AbstractPlus] and head and neck squamous cell carcinoma [http://www.ncbi.nlm.nih.gov/pubmed/21798897?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/21798893?dopt=AbstractPlus].	–	–	Notch receptor 4 is a potential therapeutic molecular target for triple‐negative breast cancer [http://www.ncbi.nlm.nih.gov/pubmed/25993190?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/24403446?dopt=AbstractPlus].

Further reading on Notch receptors

Arumugam TV et al. (2018) Notch signaling and neuronal death in stroke. Prog. Neurobiol. 165‐167: 103‐116 [https://www.ncbi.nlm.nih.gov/pubmed/29574014?dopt=AbstractPlus]

Borggrefe T et al. (2016) The Notch intracellular domain integrates signals from Wnt, Hedgehog, TGFβ/BMP and hypoxia pathways. Biochim. Biophys. Acta 1863: 303‐13 [https://www.ncbi.nlm.nih.gov/pubmed/26592459?dopt=AbstractPlus]

Palmer WH et al. (2015) Ligand‐Independent Mechanisms of Notch Activity. Trends Cell Biol. 25: 697‐707 [https://www.ncbi.nlm.nih.gov/pubmed/26437585?dopt=AbstractPlus]

Previs RA et al. (2015) Molecular pathways: translational and therapeutic implications of the Notch signaling pathway in cancer. Clin. Cancer Res. 21: 955‐61 [https://www.ncbi.nlm.nih.gov/pubmed/25388163?dopt=AbstractPlus]

Takebe N et al. (2015) Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol 12: 445‐64 [https://www.ncbi.nlm.nih.gov/pubmed/25850553?dopt=AbstractPlus]

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=891

Overview

Regulators of G protein signalling (RGS) proteins display a common RGS domain that interacts with the GTP‐bound Gα subunits of heterotrimeric G proteins, enhancing GTP hydrolysis by stabilising the transition state [http://www.ncbi.nlm.nih.gov/pubmed/8756726?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/9108480?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/9417641?dopt=AbstractPlus], leading to a termination of GPCR signalling. Interactions through protein: protein interactions of many RGS proteins have been identified for targets other than heteromeric G proteins. Sequence analysis of the 20 RGS proteins suggests four families of RGS: RZ, R4, R7 and R12 families. Many of these proteins have been identified to have effects other than through targetting G proteins. Included here is RGS4 for which a number of pharmacological inhibitors have been described.

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=892

Overview

The RZ family of RGS proteins is less well characterized than the other families [http://www.ncbi.nlm.nih.gov/pubmed/16765607?dopt=AbstractPlus]. It consists of RGS17 (also known as RGSZ2), RGS19 (also known as GAIP) and RGS20 (with several splice variants including RGSZ1 and Ret‐RGS). All members contain an N‐terminal cysteine string motif [http://www.ncbi.nlm.nih.gov/pubmed/17183362?dopt=AbstractPlus] which is a site of palmitoylation and could serve functions in membrane targeting, protein stability or aid protein‐protein interactions [http://www.ncbi.nlm.nih.gov/pubmed/17126529?dopt=AbstractPlus]. However, the function in the case of RZ family RGS proteins is not yet fully understood. Members of the RZ family of RGS proteins are the only RGS proteins that have selective GTPase activating‐protein (GAP) activity for Gα_z, a function that resulted in the name of the family [http://www.ncbi.nlm.nih.gov/pubmed/9748279?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/15096504?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/9748280?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/1347957?dopt=AbstractPlus]. However, the members of the RZ family are able to also GAP Gα_i/o members with varying selectivity.

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2801	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2802	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2803
Common abbreviation	RGS17	RGS19	RGS20
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14088, http://www.uniprot.org/uniprot/Q9UGC6	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:13735, http://www.uniprot.org/uniprot/P49795	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14600, http://www.uniprot.org/uniprot/O76081

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=893

Overview

This is the largest family of RGS proteins.

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2804	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2808	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2810	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2811
Common abbreviation	RGS1	RGS2	RGS3	RGS4
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9991, http://www.uniprot.org/uniprot/Q08116	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9998, http://www.uniprot.org/uniprot/P41220	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9999, http://www.uniprot.org/uniprot/P49796	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10000, http://www.uniprot.org/uniprot/P49798
Selective inhibitors	–	–	–	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8033 (pIC50 7.8) [http://www.ncbi.nlm.nih.gov/pubmed/22368763?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7784 (pIC50 7.5) [http://www.ncbi.nlm.nih.gov/pubmed/21329361?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8034 (pIC50 7.3) [http://www.ncbi.nlm.nih.gov/pubmed/22368763?dopt=AbstractPlus]

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2812	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2813	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2805	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2806	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2807	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2809
Common abbreviation	RGS5	RGS8	RGS13	RGS16	RGS18	RGS21
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10001, http://www.uniprot.org/uniprot/O15539	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:16810, http://www.uniprot.org/uniprot/P57771	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9995, http://www.uniprot.org/uniprot/O14921	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9997, http://www.uniprot.org/uniprot/O15492	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:14261, http://www.uniprot.org/uniprot/Q9NS28	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:26839, http://www.uniprot.org/uniprot/Q2M5E4

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=894

Overview

This family of RGS proteins shows some selectivity for Gai/o proteins.

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2815	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2816	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2817	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2814
Common abbreviation	RGS6	RGS7	RGS9	RGS11
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10002, http://www.uniprot.org/uniprot/P49758	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10003, http://www.uniprot.org/uniprot/P49802	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:10004, http://www.uniprot.org/uniprot/O75916	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9993, http://www.uniprot.org/uniprot/O94810

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=895

Overview

The R12 family consists of RGS10, 12 and 14. RGS12 and 14 are large proteins with additional domains that can participate in protein‐protein interactions and other functions. In contrast, RGS10 is a small protein consisting of the RGS domain and small N‐ and C‐termini, similar to members of the R4 family. However, sequence homology of the RGS10 RGS domain clearly places it in the R12 family [http://www.ncbi.nlm.nih.gov/pubmed/26123306?dopt=AbstractPlus]. The Gα_i/o‐Loco (GoLoco) motif in RGS12 and 14 has GDI activity (for Guanine nucleotide Dissociation Inhibitor) towards Gα_i1, Gα_i2 and Gα_i3 [http://www.ncbi.nlm.nih.gov/pubmed/11387333?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/15951850?dopt=AbstractPlus]. Through this activity RGS12 and RGS14 can inhibit G protein signaling both by accelerating GTP hydrolysis and by preventing G protein activation. Splice variants of RGS12 and RGS14 also contain membrane targeting and protein‐protein interaction domains [http://www.ncbi.nlm.nih.gov/pubmed/11130074?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/11771424?dopt=AbstractPlus, http://www.ncbi.nlm.nih.gov/pubmed/9651375?dopt=AbstractPlus].

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2818	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2819	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2820
Common abbreviation	RGS10	RGS12	RGS14
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9992, http://www.uniprot.org/uniprot/O43665	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9994, http://www.uniprot.org/uniprot/O14924	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:9996, http://www.uniprot.org/uniprot/O43566

Further reading on Regulators of G protein Signaling (RGS) proteins

Alqinyah M et al. (2018) Regulating the regulators: Epigenetic, transcriptional, and post‐translational regulation of RGS proteins. Cell. Signal. 42: 77‐87 [https://www.ncbi.nlm.nih.gov/pubmed/29042285?dopt=AbstractPlus]

Neubig RR et al. (2002) Regulators of G‐protein signalling as new central nervous system drug targets. Nat Rev Drug Discov 1: 187‐97 [https://www.ncbi.nlm.nih.gov/pubmed/12120503?dopt=AbstractPlus]

Sethakorn N et al. (2010) Non‐canonical functions of RGS proteins. Cell. Signal. 22: 1274‐81 [https://www.ncbi.nlm.nih.gov/pubmed/20363320?dopt=AbstractPlus]

Sjögren B. (2017) The evolution of regulators of G protein signalling proteins as drug targets ‐ 20 years in the making: IUPHAR Review 21. Br. J. Pharmacol. 174: 427‐437 [https://www.ncbi.nlm.nih.gov/pubmed/28098342?dopt=AbstractPlus]

Sjögren B et al. (2010) Thinking outside of the ‘RGS box’: new approaches to therapeutic targeting of regulators of G protein signaling. Mol. Pharmacol. 78: 550‐7 [https://www.ncbi.nlm.nih.gov/pubmed/20664002?dopt=AbstractPlus]

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=785

Overview

Although termed ’receptors’, the evidence for coupling through conventional signalling pathways is lacking. Initially described as a subtype of opioid receptors, there is only a modest pharmacological overlap and no structural convergence with the G protein‐coupled receptors; the crystal structure of the sigma1 receptor [http://www.ncbi.nlm.nih.gov/pubmed/27042935?dopt=AbstractPlus] suggests a trimeric structure of a single short transmembrane domain traversing the endoplasmic reticulum membrane, with the bulk of the protein facing the cytosol. A wide range of compounds, ranging from psychoactive agents to antihistamines, have been observed to bind to these sites.

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2552	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2553
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:8157, http://www.uniprot.org/uniprot/Q99720	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:28106, http://www.uniprot.org/uniprot/Q5BJF2
Agonists	–	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6684 [http://www.ncbi.nlm.nih.gov/pubmed/16463398?dopt=AbstractPlus] – Guinea pig
Selective agonists	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6678 [http://www.ncbi.nlm.nih.gov/pubmed/1658302?dopt=AbstractPlus], (http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6677	–
Antagonists	–	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6682 (pIC50 7.2) [http://www.ncbi.nlm.nih.gov/pubmed/10096443?dopt=AbstractPlus]
Selective antagonists	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6679 (pIC50 8.4) [http://www.ncbi.nlm.nih.gov/pubmed/7901723?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6680 (pIC50 7.4) [http://www.ncbi.nlm.nih.gov/pubmed/8566098?dopt=AbstractPlus]	–
Labelled ligands	[http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6683 (Agonist)	[http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6685 (Agonist)
Comments	–	The sigma2 receptor has been reported to be TMEM97 [http://www.ncbi.nlm.nih.gov/pubmed/28559337?dopt=AbstractPlus], a 4TM protein partner of NPC1, the Niemann‐Pick C1 protein, a 13TM cholesterol‐binding protein.

Comments

http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1606 also shows activity at opioid receptors. The sigma2 receptor has recently been reported to be http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2553 [http://www.ncbi.nlm.nih.gov/pubmed/28559337?dopt=AbstractPlus], a 4TM protein partner of NPC1, the Niemann‐Pick C1 protein, a 13TM cholesterol‐binding protein.

Further reading on Sigma receptors

Chu UB et al. (2016) Biochemical Pharmacology of the Sigma‐1 Receptor. Mol. Pharmacol. 89: 142‐53 [https://www.ncbi.nlm.nih.gov/pubmed/26560551?dopt=AbstractPlus]

Gris G et al. (2015) Sigma‐1 receptor and inflammatory pain. Inflamm. Res. 64: 377‐81 [https://www.ncbi.nlm.nih.gov/pubmed/25902777?dopt=AbstractPlus]

Rousseaux CG et al. (2016) Sigma receptors [σRs]: biology in normal and diseased states. J. Recept. Signal Transduct. Res. 36: 327‐388 [https://www.ncbi.nlm.nih.gov/pubmed/26056947?dopt=AbstractPlus]

Sambo DO et al. (2018) The sigma‐1 receptor as a regulator of dopamine neurotransmission: A potential therapeutic target for methamphetamine addiction. Pharmacol Ther 186: 152‐167 [https://www.ncbi.nlm.nih.gov/pubmed/29360540]

Su TP et al. (2016) The Sigma‐1 Receptor as a Pluripotent Modulator in Living Systems. Trends Pharmacol. Sci. 37: 262‐278 [https://www.ncbi.nlm.nih.gov/pubmed/26869505?dopt=AbstractPlus]

Vavers E et al. (2019) Allosteric Modulators of Sigma‐1 Receptor: A Review. Front Pharmacol 10: 223 [https://www.ncbi.nlm.nih.gov/pubmed/30941035]

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=858

Overview

Tubulins are a family of intracellular proteins most commonly associated with microtubules, part of the cytoskeleton. They are exploited for therapeutic gain in cancer chemotherapy as targets for agents derived from a variety of natural products: taxanes, colchicine and vinca alkaloids. These are thought to act primarily through β‐tubulin, thereby interfering with the normal processes of tubulin polymer formation and disassembly.

Nomenclature	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2638	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2639	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2640	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2752	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2641	http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2753
HGNC, UniProt	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:20766, http://www.uniprot.org/uniprot/Q71U36	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:12407, http://www.uniprot.org/uniprot/P68366	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:20778, http://www.uniprot.org/uniprot/P07437	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:20772, http://www.uniprot.org/uniprot/Q13509	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:20771, http://www.uniprot.org/uniprot/P68371	https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:20773, http://www.uniprot.org/uniprot/Q3ZCM7
Inhibitors	–	–	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6851 (pIC50 9), http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6813 (pIC50 8.2) [http://www.ncbi.nlm.nih.gov/pubmed/21324687?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2770 (Mitotic cell cycle arrest in A431 cells) (pEC50 8.1) [http://www.ncbi.nlm.nih.gov/pubmed/16377187?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2367 (pIC50 8) [http://www.ncbi.nlm.nih.gov/pubmed/16504507?dopt=AbstractPlus], http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6798, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6809, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6824, http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=6785	http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=8854 (pIC50 8.2) [http://www.ncbi.nlm.nih.gov/pubmed/23895532?dopt=AbstractPlus]	–	–

Further reading on Tubulins

Arnst KE et al. (2019) Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy. Med Res Rev 39: 1398‐1426 [https://www.ncbi.nlm.nih.gov/pubmed/30746734]

Eshun‐Wilson L. (2019) Effects of alpha‐tubulin acetylation on microtubule structure and stability. Proc Natl Acad Sci U S A 116: 10366‐10371 [https://www.ncbi.nlm.nih.gov/pubmed/31072936]

Gadadhar S et al. (2017) The tubulin code at a glance. J. Cell. Sci. 130: 1347‐1353 [https://www.ncbi.nlm.nih.gov/pubmed/28325758?dopt=AbstractPlus]

Magiera MM et al. (2018) Tubulin Posttranslational Modifications and Emerging Links to Human Disease. Cell 173: 1323‐1327 [https://www.ncbi.nlm.nih.gov/pubmed/29856952]

Penna LS et al. (2017) Anti‐mitotic agents: Are they emerging molecules for cancer treatment? Pharmacol. Ther. 173: 67‐82 [https://www.ncbi.nlm.nih.gov/pubmed/28174095?dopt=AbstractPlus]

Alexander Stephen PH, Kelly Eamonn, Mathie Alistair, Peters John A, Veale Emma L, Faccenda Elena, Harding Simon D, Pawson Adam J, Sharman Joanna L, Southan Christopher, Buneman O Peter, Cidlowski John A, Christopoulos Arthur, Davenport Anthony P, Fabbro Doriano, Spedding Michael, Striessnig Jörg, Davies Jamie A and CGTP Collaborators (2019) THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Introduction and Other Protein Targets. British Journal of Pharmacology, 176: S1–S20. doi: 10.1111/bph.14747.