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

Table 1.

Single-component drugs targeting extracellular factors.

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Pomalidomide Inhibitor Small molecule IPF Approved| 2(withdrawn) NCT01135199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.

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

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.