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. 2017 Nov 23;8:855. doi: 10.3389/fphar.2017.00855

Table 2.

Single-component drugs targeting intracellular factors.

Target Drug Clinical trialb Reference
Group Target or mechanism type Target or mechanism Organsa Drug Name Mechanism Class Disease Phase Reference/Trial identifierc
Enzymes mTORd mTORC1/2d Liver, Kidney, Lung, Heart, Skin, Gut Rapamycin (Sirolimus)* Inhibitor Small molecule Renal interstitial fibrosis Approved| 3(completed) NCT01079143
Palomid-529 (RES-529) Inhibitor Small molecule Macular degeneration 1(completed) NCT01033721
JAK-STATd JAK1/JAK2d Ruxolitinib Inhibitor Small molecule Myelofibrosis Approved| 3(completed) NCT00952289
Baricitinib Inhibitor Small molecule Renal interstitial fibrosis Preclinical Breyer and Susztak, 2016
PI3K-Aktd Akt Liver, Kidney, Lung, Heart, Skin Omipalisib (GSK2126458) Inhibitor Small molecule IPFd 1(completed) NCT01725139
FAK1d Liver, Kidney, Lung, Heart, Pancreas, Skin PF-562271 Inhibitor Small molecule Pulmonary fibrosis; Cardiac fibrosis; Liver fibrosis Preclinical Lagares et al., 2012; Fan et al., 2015; Zhao et al., 2017
MAPKd JNKd Tanzisertib (CC-930) Inhibitor Small molecule IPF 2(terminated) NCT01203943
MAPK Liver, Kidney, Lung, Heart, Pancreas, Skin, Gut MMI-0100 Inhibitor Small molecule IPF; Cardiac fibrosis Preclinical Xu et al., 2014
NF-κBd IKKd IMD-1041 Inhibitor Small molecule Cardiac fibrosis Preclinical Tanaka et al., 2012
Bardoxolone methyl (CDDO-Me) Inhibitor Small molecule Pulmonary hypertension 2(recruiting) NCT02036970
NF-κB Antisense NF-κB Inhibitor Antisense oligonucleotide Intestinal fibrosis Preclinical Lawrance et al., 2003
Baicalein* Inhibitor Small molecule Renal fibrosis; IPF Preclinical Gao et al., 2013; Wang et al., 2015
Sulfasalazine Inhibitor Small molecule Liver fibrosis; Pancreatic fibrosis Approved| Preclinical Chavez et al., 2012; Wang et al., 2016
cAMP-PKAd ROCKd Y-27632 Inhibitor Small molecule Renal fibrosis; Liver fibrosis Preclinical Tada et al., 2001
Non-kinase enzyme 26S protease Liver, Kidney, Lung, Heart Bortezomib Inhibitor Small molecule SSc pulmonary fibrosis Approved| 2(recruiting) NCT02370693
Caspase Liver, Kidney, Lung, Heart, Skin Emricasan Inhibitor Small molecule Liver fibrosis Preclinical Barreyro et al., 2015
VX-166 Inhibitor Small molecule Liver fibrosis Preclinical Witek et al., 2009
Z-VAD-fmk Inhibitor Small molecule Pulmonary fibrosis Preclinical Kuwano et al., 2001
PDEd Kidney, Heart CTP-499 Inhibitor Small molecule Diabetic nephropathy 1(completed) NCT01328821
Cathepsin B Liver, Lung, Heart, Pancreas VBY-376 Inhibitor Small molecule Liver fibrosis Preclinical Alkhouri et al., 2011
CA-074Me Inhibitor Small molecule Pancreatic fibrosis; Cardiac fibrosis; Pulmonary fibrosis Preclinical Lerch and Halangk, 2006; Liu et al., 2013; Zhang et al., 2015
S100A9 Liver, Lung, Heart, Skin Paquinimod Inhibitor Small molecule SScd 2(completed) NCT01487551
Procollagen-proline dioxygenase Liver, Lung HOE-077 Inhibitor Small molecule Liver fibrosis Preclinical Matsumura et al., 1997
Nuclear receptors PPARd PPAR-γ Liver, Kidney, Lung, Heart, Pancreas, Skin, Gut Rosiglitazone Agonist Small molecule Liver fibrosis; Approved| 2(completed) NCT00492700
Elafibranor (GFT-505) Agonist Small molecule Liver fibrosis 3(recruiting) NCT02704403
Saroglitazar Agonist Small molecule Liver fibrosis 2(recruiting) NCT03061721
Pioglitazone Agonist Small molecule Cystic fibrosis; Liver fibrosis Approved| 1(completed); 1(completed) NCT00719381; NCT01454336
Docosahexaenoic acid* Agonist Small molecule Liver fibrosis; Pulmonary fibrosis Preclinical Depner et al., 2013; Zhao et al., 2014
FXRd FXR Liver, Kidney, Lung, Gut INT-767 Agonist Small molecule Liver fibrosis Preclinical Baghdasaryan et al., 2011
PX-102 Agonist Small molecule Liver fibrosis Preclinical Ali et al., 2015
Obeticholic acid* (INT-747) Agonist Small molecule Liver fibrosis Approved| 3(recruiting) NCT02548351
Turofexorate isopropyl (WAY-362450) Agonist Small molecule Liver fibrosis Preclinical Zhang et al., 2009
GW4064 Agonist Small molecule Liver fibrosis Preclinical Liu et al., 2003
GRd GR Liver, Lung, Heart, Skin Triamcinolone Agonist Small molecule Keloid scarring Approved| 1(terminated) NCT01978301
ERd ERβ Liver Genistein* Agonist Small molecule Pulmonary fibrosis; Liver fibrosis Preclinical Salas et al., 2008; Nadadur et al., 2012
Other proteins Intracellular TGF-βd signaling SMAD2/3 Liver, Kidney, Lung, Heart, Pancreas, Skin, Gut Pirfenidone Inhibitor Small molecule IPF; SSc Approved| 3(completed); 2(completed) NCT00287729; NCT01933334
SMAD3/4 Pentoxifylline Inhibitor Small molecule Skin fibrosis Approved| 2(completed) NCT00001437
SMAD3 SIS-3 Inhibitor Small molecule Renal fibrosis Preclinical Meng et al., 2015
Glycyrrhizin* Inhibitor Small molecule Liver fibrosis 3(terminated) NCT00686881
Epigenetics miRNA miR-21 Anti-miR-21 Inhibitor Oligonucleotide IPF; Renal fibrosis Preclinical Liu et al., 2010; Chau et al., 2012
methylation Transmethylation Liver, Kidney, Lung, Heart, Skin, Gut Ademetionine (SAM) Inhibitor Small molecule Liver fibrosis Approved| Unknown NCT02231333
BMPER (gene) Lung DNA methylation Inhibitor Methylation IPF Preclinical Huan et al., 2015
*

Drug belongs to monomer extracted from natural products.

a

Organs that had study report of corresponding targets in fibrosis treatment.

b

Clinical trial resource are from http://Clinicaltrials.gov.

c

Trial Identifier is the clinical trail identifier of corresponding drug.

d

mTOR, mechanistic target of rapamycin; mTORC1, mechanistic target of rapamycin complex 1; JAK-STAT, janus kinase/signal transducers and activators of transcription; PI3K-Akt, phosphoinositide 3-kinase/protein kinase B; IPF, idiopathic pulmonary fibrosis; FAK1, focal adhesion kinase 1; MAPK, mitogen-activated protein kinase; JNK, c-Jun N-terminal kinases; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; IKK, I-kappa B kinase; cAMP-PKA, cyclic AMP- protein kinase A signaling; ROCK, rho-associated protein kinase; PDE, phosphodiesterase; SSc, systematic sclerosis; PPAR, peroxisome proliferator-activated receptor; FXR, farnesoid X receptor; GR, glucocorticoid receptor; ER, estrogen receptor; TGF-β, transforming growth factor-β.