Table 1. Screening in vitro of MCA-13 effects on selected GPCRs, ion channels, kinases, nuclear hormone receptors, enzymes and neurotransmitter transporters.
| Target Protein name | Target Gene name | Reference Compound1 | Mode of action2 | Functional Assay3 | RC50(μM)4 | MCA-13 Max. Responce (%)5 |
|---|---|---|---|---|---|---|
| GPCRs | ||||||
| Adenosine Receptor A2A | ADORA2A | NECA | Agonist | Calcium Flux | 0.01524 | 0 |
| SCH 442416 | Antagonist | 0.04332 | 4.09 | |||
| Adrenergic Receptor α1A | ADRA1A | A61603 | Agonist | Calcium Flux | 0.0011 | 1.12 |
| Tamsulosin | Antagonist | 0.00096 | 3.06 | |||
| Adrenergic Receptor α2A | ADRA2A | UK 14304 | Agonist | cAMP | 0.00066 | 24.55 |
| Yohimbine | Antagonist | 0.02617 | 0 | |||
| Adrenergic Receptor β1 | ADRB1 | Isoproterenol | Agonist | cAMP | 0.00125 | 1.92 |
| Betaxolol | Antagonist | 0.02278 | 9.29 | |||
| Adrenergic Receptor β2 | ADRB2 | Isoproterenol | Agonist | cAMP | 0.0016 | 1.29 |
| ICI 118,551 | Antagonist | 0.00211 | 8.23 | |||
| Arginine Vasopressin Receptor 1A | AVPR1A | [Arg8]-Vasopressin | Agonist | Calcium Flux | 0.00052 | 0.29 |
| SR49059 | Antagonist | 0.0029 | 0 | |||
| Cholecystokinin Receptor A | CCKAR | (Tyr[SO3H]27) Cholecystokinin Fragment 26–33 Amide | Agonist | Calcium Flux | 0.0002 | 1.56 |
| SR 27897 | Antagonist | 0.0298 | 0 | |||
| Muscarinic acetylcholine Receptor M1 | CHRM1 | Acetylcholine chloride | Agonist | Calcium Flux | 0.02359 | 0 |
| Atropine | Antagonist | 0.00695 | 7.43 | |||
| Muscarinic acetylcholine Receptor M2 | CHRM2 | Acetylcholine chloride | Agonist | cAMP | 0.02725 | 11.68 |
| Atropine | Antagonist | 0.01538 | 0 | |||
| Muscarinic acetylcholine Receptor M3 | CHRM3 | Acetylcholine chloride | Agonist | Calcium Flux | 0.04944 | 0.13 |
| Atropine | Antagonist | 0.00612 | 8.81 | |||
| Cannabinoid Receptor 1 | CNR1 | CP 55940 | Agonist | cAMP | 0.00012 | 50.22 |
| AM251 | Antagonist | 0.00466 | 0.57 | |||
| Cannabinoid Receptor 2 | CNR2 | CP55940 | Agonist | cAMP | 0.00033 | 49.59 |
| SR144528 | Antagonist | 0.0491 | 4.11 | |||
| Dopamine Receptor D1 | DRD1 | Dopamine | Agonist | cAMP | 0.17552 | 0 |
| SCH 39166 | Antagonist | 0.0026 | 14.3 | |||
| Dopamine Receptor D2 | DRD2S | Dopamine | Agonist | cAMP | 0.00321 | 0 |
| Risperidone | Antagonist | 0.00589 | 0.51 | |||
| Endothelin Receptor Type A | EDNRA | Endothelin 1 | Agonist | Calcium Flux | 0.00036 | 0 |
| BMS 182874 | Antagonist | 0.63689 | 0 | |||
| Histamine Receptor H1 | HRH1 | Histamine | Agonist | Calcium Flux | 0.0155 | 0 |
| Mepyramine | Antagonist | 0.01549 | 1.05 | |||
| Histamine Receptor H2 | HRH2 | Histamine | Agonist | cAMP | 1.01395 | 1.78 |
| Tiotidine | Antagonist | 0.06593 | 26.94 | |||
| 5-Hydroxy tryptamine (Serotonin) Receptor 1A | HTR1A | Serotonin Hydrochloride | Agonist | cAMP | 0.01101 | 7.66 |
| Spiperone | Antagonist | 0.08756 | 0 | |||
| 5-Hydroxy tryptamine (Serotonin) Receptor 1B | HTR1B | Serotonin Hydrochloride | Agonist | cAMP | 0.0046 | 10.47 |
| SB 224289 | Antagonist | 0.03853 | 0 | |||
| 5-Hydroxy tryptamine (Serotonin) Receptor 2A | HTR2A | Serotonin Hydrochloride | Agonist | Calcium Flux | 0.0061 | 1.13 |
| Altanserin | Antagonist | 0.01903 | 0 | |||
| 5-Hydroxy tryptamine (Serotonin) Receptor 2B | HTR2B | Serotonin Hydrochloride | Agonist | Calcium Flux | 0.00263 | 0 |
| LY 272015 | Antagonist | 0.00082 | 0.13 | |||
| Opioid Receptor Delta 1 | OPRD1 | DADLE | Agonist | cAMP | 0.00012 | 6.34 |
| Naltriben | Antagonist | 0.00064 | 0 | |||
| Opioid Receptor Kappa 1 | OPRK1 | Dynorphin A (1–17) | Agonist | cAMP | 0.0481 | 7.89 |
| Nor- Binaltorphimine | Antagonist | 0.0064 | 0 | |||
| Opioid Receptor Mu 1 | OPRM1 | DAMGO | Agonist | cAMP | 0.00194 | 9.31 |
| Naloxone | Antagonist | 0.00552 | 0.38 | |||
| Target Protein name | Target Gene name | Reference Compound1 | Mode of action2 | Functional Assay3 | RC50(μM)4 | MCA-13 Max. Responce (%)5 |
|---|---|---|---|---|---|---|
| Ion channels | ||||||
| Voltage-gated L-type calcium channel | CAV1.2 | Isradipine | Blocker | Ion channel | 0.0225 | 3.82 |
| Gamma-aminobutyric acid Receptor A | GABAA | Picrotoxin | Blocker | 5.91692 | 7.74 | |
| GABA | Opener | 8.51412 | 3.68 | |||
| Kv11.1, the alpha subunit of a potassium ion channel | hERG | Astemizole | Blocker | 0.07136 | 0 | |
| 5-Hydroxy-tryptamine (Serotonin) Receptor 3A | HTR3A | Bemestetron | Blocker | 0.00368 | 0.19 | |
| Serotonin Hydrochloride | Opener | 0.552217 | 0 | |||
| Kv7.1/KCNE Potassium voltage-gated channel | KvLQT1/minK | XE 991 | Blocker | 2.63679 | 0.55 | |
| ML-277 | Opener | 6.71743 | 0 | |||
| Nicotinic acetylcholine Receptor alpha-4 beta-2 | nAChR(a4/b2) | Dihydro-AY-erythroidine | Blocker | 0.70659 | 5.95 | |
| Nicotine | Opener | 2.18712 | 0 | |||
| A tetrodotoxin-resistant voltage-gated sodium channel | NAVI1.5 | Lidocaine | Blocker | 41.01752 | 0 | |
| N-methyl-d-aspartate (NMDA) Glutamate Receptor 1A/2B | NMDAR (1A/2B) | MK 801 | Blocker | 0.05277 | 0 | |
| l-Glutamic Acid | Opener | 0.96247 | 0 | |||
| Kinases | ||||||
| Insulin Receptor | INSR | BMS-754807 | Inhibitor | Binding | 0.0009 | 3.22 |
| (tyrosine kinase) | ||||||
| Lymphocyte Cell-Specific Protein-Tyrosine Kinase (Src family) | LCK | Gleevec | Inhibitor | 0.07191 | 12.77 | |
| Rho Associated Coiled-Coil Containing Protein Kinase 1 (serine-threonine kinase) | ROCK1 | Staurosporine | Inhibitor | 0.00034 | 21.61 | |
| Vascular endothelial growth factor receptor 2 (KDR tyrosine kinase) | VEGFR2 | SU-11248 | Inhibitor | 0.00033 | 21.68 | |
| Nuclear Hormone Receptors | ||||||
| Nuclear Hormone Androgen Receptor | AR | 6a-Fluorotestosterone | Agonist | Nuclear Hormone Receptor | 0.00646 | 0 |
| Geldanamycin | Antagonist | 0.08646 | 5.27 | |||
| Nuclear Hormone Glucocorticoid Receptor | GR | Dexamethasone | Agonist | 0.10198 | 0 | |
| Mifepristone | Antagonist | 0.10906 | 2.28 | |||
| Enzymes | ||||||
| Acetylcholinesterase | AChE | Physostigmine | Inhibitor | Enzymatic | 0.0282 | 4.27 |
| Cyclooxygenase 1 | COX 1 | Indomethacin | Inhibitor | 0.06281 | 24.99 | |
| Cyclooxygenase 2 | COX 2 | NS −398 | Inhibitor | 0.07376 | 7.99 | |
| Monoamine oxidase type A | MAOA | Clorgyline | Inhibitor | 0.00217 | 1.86 | |
| cGMP-inhibited cyclic nucleotide phospho-diesterase 3A | PDE3A | Cilostamide | Inhibitor | 0.02113 | 3.21 | |
| cAMP-specific 3′,5′-cyclic phospho-diesterase 4D2 | PDE4D2 | Cilomilast | Inhibitor | 0.01549 | 0 | |
| Catecholamine Transporters | ||||||
| Dopamine transporter | DAT | GBR 12909 | Blocker | Transporter | 0.0076 | 0 |
| Norepinephrine transporter | NET | Desipramine | Blocker | 0.01089 | 3.53 | |
| Serotonin transporter | SERT | Clomipramine | Blocker | 0.00878 | 15.45 | |
Full chemical names of reference compounds: NECA, 5′-(N-Ethylcarboxamido)adenosine; SCH 442416, 2-(2-furyl)-7-[3-(4-methoxyphenyl)propyl]-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine;A61603, N-(5-(4,5-Dihydro-1H-imidazol-2-yl)-2-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)methanesulfonamide hydrobromide; Tamsulosin, 5-(2-((2-Ethoxyphenoxy)ethyl)amino) propyl −2-methoxybenzenesulfonamide; UK 14304, 5-Bromo-N-(2-imidazolin-2-yl)-6-quinoxalinamine; Yohimbine, methyl (1S,15R,18S,19R,20S)-18-hydroxy1,3,11,12,14,15, 16,17,18,19,20,21- dodecahydroyohimban-19-carboxylate; Isoproterenol, 4-[1-hydroxy-2-(propan-2-ylamino)ethyl]benzene-1,2-diol;Betaxolol, 1-[4-[2-(cyclopropylmethoxy)ethyl ]phenoxy]-3-(propan-2-ylamino)propan-2-ol; Isoproterenol, 4-[1-hydroxy-2-(propan-2-ylamino)ethyl]benzene-1,2-diol; ICI 118551, (2R,3S)-1-[(7-methyl-2,3-dihydro-1H-inden-4-yl)oxy]-3-(propan-2-ylamino)butan-2-ol;hydrochloride; SR49059, (2S)-1-[[(2R,3S)-5-Chloro-3-(2-chlorophenyl)-1-[(3,4-dimethoxyphenyl)sulfonyl]-2,3-dihydro-3-hydroxy-1H-indol-2-yl]carbonyl]-2-pyrrolidinecarboxamide; SR 27897, 2-[[[4-(2-chlorophenyl)-2-thiazolyl]amino]carbonyl]-1H-indole-1-acetic acid; CP 55940, 5-(1,1-Dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol; CP55940, 5-(1,1-Dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]phenol; AM251, 1-(2,4-Dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide; SR144528, 5-(4-Chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide; SCH 39166, (6aS-trans)-11-Chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5H-benzo[d]naphth[2,1-b]azepin-12-ol hydrobromide; BMS 182874, 5-(Dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide hydrochloride; SB 224289, 1′-Methyl-5-[[2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4′-piperidine hydrochloride; LY 272015, 1-[(3,4-Dimethoxyphenyl)methy]-2,3,4,9-tetrahydro-6-methyl-1H-pyrido[3,4-b]indole hydrochloride; XE 991, 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone; ML-277, (2R)-N-[4-(4-Methoxyphenyl)-2-thiazolyl]-1-[(4-methylphenyl)sulfonyl]-2-piperidinecarboxamide; MK 801, (2R)-N-[4-(4-Methoxyphenyl)-2-thiazolyl]-1-[(4-methylphenyl)sulfonyl]-2-piperidinecarboxamide; BMS-754807, (2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoropyridin-3-yl)-2-methylpyrrolidine-2-carboxamide; SU-11248, N-[2-(Diethylamino)ethyl]-5-[(Z)-(5-fluoro-1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide (2S)-2-hydroxybutanedioic acid; NS −398, 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide; GBR 12909, 1-(2-[bis(4-Fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine dihydrochloride.
The mode of interaction with the biological target.
The assay describing the major function of the biological target.
Reference compound effective concentration 50%.
HU-MCA- 13 maximal response (activation or inhibition) at a concentration of 10 μM.