Table 2.
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.
Organs that had study report of corresponding targets in fibrosis treatment.
Clinical trial resource are from http://Clinicaltrials.gov.
Trial Identifier is the clinical trail identifier of corresponding drug.
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.