Table 1.
Target | Drug | Clinical trialb | Reference | ||||||
---|---|---|---|---|---|---|---|---|---|
Group | Target or mechanism type | Target or mechanism | Organsa | Drug Name | Mechanism | Class | Disease | Phase | Reference/Trial identifierc |
Growth factors | Extracellular TGF-β signaling | TGF-βd | Liver, Kidney, Lung, Heart, Pancreas, Skin, Gut | SHP-627 (FT011) | Inhibitor | Small molecule | Cardiac fibrosis | Preclinical | Zhang et al., 2012 |
Hydronidone (F351) | Inhibitor | Small molecule | Liver fibrosis | 2(unknown) | NCT02499562 | ||||
PXS-25 | Inhibitor | Small molecule | IPFd | Preclinical | Maldonado et al., 2009; Wong et al., 2011 | ||||
Disitertide (P-144) | Inhibitor | Small molecule | Skin fibrosis | 2(completed) | NCT00574613 | ||||
Fresolimumab (GC-1008) | Inhibitor | Monoclonal antibody | IPF; SScd | 1(completed); 1(completed) | NCT00125385; NCT01284322 | ||||
LY2382770 | Inhibitor | Monoclonal antibody | Diabetic kidney disease | 2(terminated) | NCT01113801 | ||||
Integrin αvβ6 | STX-100 | Inhibitor | Monoclonal antibody | IPF | 2(completed) | NCT01371305 | |||
CWHM-12 | Inhibitor | Small molecule | Liver fibrosis; Lung fibrosis | Preclinical | Henderson et al., 2013 | ||||
ALK5d | SB-431542 | Antagonist | Small molecule | Pulmonary fibrosis | Preclinical | Koh et al., 2015 | |||
BMP-7d | THR-184 | Agonist | Small molecule | Renal fibrosis | 2(completed) | NCT01830920 | |||
CTGFd | CTGF | PF-06473871 | Inhibitor | Small molecule | Hypertrophic scar | 2(completed) | NCT01730339 | ||
RXI-109 | Inhibitor | Small molecule | Hypertrophic scar | 2(completed) | NCT02030275 | ||||
FG-3019 | Inhibitor | Monoclonal antibody | IPF | 2(active, not recruiting) | NCT01890265 | ||||
PDGFd/VEGFd | PDGFRd | Imatinib | Antagonist | Small molecule | Nephrogenic systemic fibrosis; SSc; IPF | Approved| 2(completed); 2(completed); 3(completed) | NCT00677092; NCT00613171; NCT00131274 | ||
BOT-191 | Antagonist | Small molecule | Liver fibrosis | Preclinical | van Dijk et al., 2015 | ||||
Nilotinib (AMN-107) | Antagonist | Small molecule | SSc | Approved| 2(completed) | NCT01166139 | ||||
Dasatinib | Antagonist | Small molecule | Scleroderma pulmonary fibrosis | Approved| 2(completed) | NCT00764309 | ||||
VEGFRd/PDGFR | Nintedanib (BIBF-1120) | Antagonist | Small molecule | Scleroderma; IPF | Approved| 3(recruiting); 3(completed) | NCT02597933; NCT01335464 | |||
Sorafenib (BAY 43-9006) | Antagonist | Small molecule | Extensive keloids | Approved| 2(terminated) | NCT01425216 | ||||
TNFd | TNF | Thalidomide | Inhibitor | Small molecule | IPF | Approved| 2(completed) | NCT00162760 | ||
Pomalidomide | Inhibitor | Small molecule | IPF | Approved| 2(withdrawn) | NCT01135199 | ||||
Etanercept | Inhibitor | Recombinant protein | IPF | Approved| 2(completed) | NCT00063869 | ||||
Belimumab | Inhibitor | Monoclonal antibody | SSc | Approved| 2(completed) | NCT01670565 | ||||
HGFd | HGF | Liver, Kidney, Lung, Heart, Skin | Refanalin (BB-3) | Stimulant | Small molecule | Liver fibrosis; IPF | Preclinical | Fallowfield, 2011 | |
Cytokines | Interleukin | IL-13d | Liver, Kidney, Lung, Heart, Pancreas, Skin, Gut | Dectrekumab (QAX-576) | Inhibitor | Monoclonal antibody | IPF; IPF secondary to SSc | 2(terminated); 2(terminated) | NCT01266135; NCT00581997 |
Tralokinumab | Inhibitor | Monoclonal antibody | IPF | 2(terminated) | NCT01629667 | ||||
IL-1R1 | Liver, Kidney, Lung, Heart, Skin, Gut | Anakinra | Antagonist | Recombinant protein | Cystic fibrosis | Approved| Preclinical | Iannitti et al., 2016 | ||
IL-1βR | Rilonacept | Antagonist | Recombinant protein | SSc | Approved| 2(active, not recruiting) | NCT01538719 | |||
IL-13/IL-4 | SAR156597 | Inhibitor | Monoclonal antibody | SSc; IPF | 2(recruiting); 2(completed) | NCT02921971; NCT01529853 | |||
CC chemokine | CCL2d | Liver, Kidney, Lung, Heart, Pancreas, Skin, Gut | Carlumab (CNTO-888) | Inhibitor | Monoclonal antibody | IPF | 2(completed) | NCT00786201 | |
Bindarit | Inhibitor | Small molecule | Myocardial fibrosis; Renal fibrosis | Preclinical | Lin et al., 2009; Zhu et al., 2009 | ||||
CCR5d | Liver, Kidney, Lung | Maraviroc | Antagonist | Small molecule | Liver fibrosis | Approved| Preclinical | Gonzalez et al., 2014 | ||
CCR2 | Liver, Kidney, Lung, Heart, Pancreas, Skin, Gut | RS-504393 | Antagonist | Small molecule | Renal fibrosis | Preclinical | Kitagawa et al., 2004 | ||
Interferon | IFN-γRd | Actimmune | Stimulant | Interferon | IPF; Liver fibrosis; Cystic fibrosis | Approved| 3(completed); 2(completed); 2(completed) | NCT00047658; NCT00043303; NCT00043316 | ||
IFN-α | Liver, Kidney, Lung | Interferon alpha oral lozenge | Stimulant | Interferon | Pulmonary fibrosis | 2(completed) | NCT01442779 | ||
MMPd/TIMPd | MMP/TIMP | MMP-2/MMP-9/TIMP-1 | Liver, Kidney, Lung, Heart, Pancreas, Skin, Gut | Batimastat(BB-49) | Inhibitor | Small molecule | IPF | Preclinical | Corbel et al., 2001 |
MMP/TIMP | Marimastat | Inhibitor | Small molecule | Liver fibrosis | Approved| Preclinical | de Meijer et al., 2010 | |||
Other proteins and peptides | Endothelin | ET-1 receptord | Liver, Kidney, Lung, Heart, Skin, Gut | Macitentan | Antagonist | Small molecule | IPF | Approved| 2(completed) | NCT00903331 |
Bosentan | Antagonist | Small molecule | IPF; SSc; | Approved| 3(completed); 3(completed); 4(completed) | NCT00070590; NCT00319696; NCT01395732 | ||||
Ambrisentan | Antagonist | Small molecule | IPF; SSc | Approved| 3(terminated); 4(unknown) | NCT00879229; NCT01051960 | ||||
Sparsentan (RE-021) | Antagonist | Small molecule | Focal segmental glomerulosclerosis | 2(active, not recruiting) | NCT01613118 | ||||
Atrasentan | Antagonist | Small molecule | Renal fibrosis | Preclinical | Samad et al., 2015 | ||||
Angiotensin II | AT1 receptord | Liver, Kidney, Lung, Heart, Pancreas, Skin, Gut | Losartan | Antagonist | Small molecule | Liver fibrosis; Cystic fibrosis | Approved| 4(completed); 2(not yet recruiting) | NCT00298714; NCT03206788 | |
GPCRd | LPARd | Liver, Kidney, Lung, Skin | BMS-986020 | Antagonist | Small molecule | SSc; IPF | 2(withdrawn); 2(completed) | NCT02588625; NCT01766817 | |
SAR-100842 | Antagonist | Small molecule | SSc | 2(completed) | NCT01651143 | ||||
PAR1d | Liver, Kidney, Lung, Heart, Pancreas, Skin | PAR1 antagonism | Antagonist | Small molecule | Liver fibrosis | Preclinical | Fiorucci et al., 2004 | ||
CB1 receptord | Liver | Curcumin* | Antagonist | Small molecule | Liver fibrosis; Renal fibrosis; IPF | Preclinical | Smith et al., 2010; Zhang et al., 2013; Sun et al., 2017 | ||
Silymarin* | Antagonist | Small molecule | Liver fibrosis | Preclinical | Tsai et al., 2008; Zhang et al., 2013 | ||||
CB2 receptord | β-caryophyllene* | Agonist | Small molecule | Liver fibrosis | Preclinical | Calleja et al., 2013; Mahmoud et al., 2014 | |||
Prostacyclin receptor | Liver, Kidney, Lung, Heart, Pancreas | Beraprost | Agonist | Small molecule | Renal fibrosis; Cardiac fibrosis | Preclinical | Chen et al., 2014 | ||
Iloprost | Agonist | Small molecule | SSc | Approved| 2(completed) | NCT00109681 | ||||
Treprostinil | Agonist | Small molecule | IPF; SSc | Approved| 2(terminated); 2(completed) | NCT00703339; NCT00775463 | ||||
VIP receptor | Lung | Aviptadil | Agonist | Peptide hormone | Cystic fibrosis | Preclinical | Mathioudakis et al., 2013 | ||
Leukocyte elastase | Leukocyte elastase | Sivelestat | Inhibitor | Small molecule | IPF | Preclinical | Takemasa et al., 2012 | ||
TAFId | TAFI | Liver, Kidney, Lung | UK-396082 | Inhibitor | Small molecule | Renal fibrosis | Preclinical | Atkinson et al., 2015 | |
Relaxin | Relaxin receptor | Liver, Kidney, Lung, Heart, Skin | Serelaxin | Stimulant | Peptide hormone | Cardiac fibrosis; Renal fibrosis | Preclinical | Samuel et al., 2014; Huuskes et al., 2015 | |
SAPd | SAP (mimic) | PRM-151 | Stimulant | Recombinant protein | IPF | 2(active, not recruiting) | NCT02550873 | ||
Integrin α | Integrin α5 | Liver | Dioscin* | Inhibitor | Small molecule | Liver fibrosis | Preclinical | Liu et al., 2015; Zhang et al., 2015a,b; Gu et al., 2016; Xu et al., 2017; Yin et al., 2017 | |
TGMd | TGM2 | Kidney, Lung | NTU281 | Inhibitor | Small molecule | Renal fibrosis | Preclinical | Johnson et al., 2007 |
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
TGF-β, transforming growth factor-β; IPF, idiopathic pulmonary fibrosis; SSc, systematic sclerosis; ALK5, TGF-β receptor 1; BMP-7, bone morphogenetic protein 7; CTGF, connective tissue growth factor; PDGF, platelet-derived growth factor; PDGFR, platelet-derived growth factor receptor; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; TNF, tumor necrosis factor; HGF, hepatocyte growth factor; IL-13, interleukin-13; CCL2, chemokine (C-C motif) ligand 2; CCR5, C-C chemokine receptor type 5; IFN-γR, interferon-γ receptor; MMP, matrix metalloproteinase; TIMP, tissue inhibitor of metalloproteinase; ET-1 receptor, endothelin-1 receptor; AT1 receptor, angiotensin II receptor type 1; GPCR, G protein-coupled receptor; LPAR, lysophosphatidic acid receptor; PAR1, protease-activated receptor 1; CB1 receptor, cannabinoid receptor type 1; TAFI, thrombin activatable fibrinolysis inhibitor; SAP, serum amyloid P; VIP, vasoactive intestinal peptide; TGM2, transglutaminase.