. Author manuscript; available in PMC: 2013 Jan 6.

Published in final edited form as: Nat Med. 2012 Jul 6;18(7):1028–1040. doi: 10.1038/nm.2807

Table 1.

Antifibrotic strategies between bench and clinic

Category	Name	Target/mechanism	Class	Target disease	Manufacturer	Phase
Growth factors	Pirfenidone	TGF-β activity, inflammation	Small molecule	IPF, hepatic and renal fibroses, hypertrophic cardiomyopathy	InterMune	Clinic^a
	GC1008	TGF-β1	Monoclonal antibody	Myelofibrosis, systemic sclerosis	Genzyme	1
	LY2382770	TGF-β1	Monoclonal antibody	Diabetic glomerulosclerosis	Eli Lilly and Company	2
	FG-3019	CTGF	Monoclonal antibody, antisense	IPF, scar-revision surgery	FibroGen	1/2
	PRM-151	SAP (pentraxin 2)	Recombinant protein	IPF, post-surgical scarring	Promedior	1/2
ECM	GS-6624	Lysyl oxidase–like-2	Monoclonal antibody, small molecule	Cardiac fibrosis, IPF	Gilead Sciences	1/2
	STX-100	Integrin α_vβ₆	Monoclonal antibody	IPF, renal fibrosis	Stromedix	1
Intracellular enzymes	Sivelestat	Neutrophil elastase	Small molecule	Acute lung injury, chronic obstructive pulmonary disease, IPF	Ono Pharmaceutical	1
	FG-4592	Hypoxia-inducible factor prolyl hydroxylase	Small molecule	Chronic kidney disease	FibroGen	2
	Bortezomib	26S proteasome	Small molecule	Pulmonary and dermal fibrosis	Millennium	Clinic^b
	Imatinib	PDGFR tyrosine kinase	Small molecule	Nephrogenic systemic fibrosis	Novartis	2
	Sirolimus	Mammalian target of rapamycin (mTOR)	Small molecule	Renal fibrosis, IPF	Pfizer	3/4^c
	BIBF 1120^d	Angiokinases	Small molecule	IPF	Boehringer Ingelheim	2
	INCB018424	Jak2	Small molecule	Myelofibrosis	Sanofi-Aventis	1/2
	CC-930	JNK	Small molecule	IPF	Celgene	2
Immunomodulators/ Inflammatory modulators	Etanercept	TNF-α	TNF receptor 2–IgG1 fusion protein	IPF	Pfizer	2
	QAX576	IL-13	Monoclonal antibody	IPF, eosinophilic esophagitis, asthma	Novartis	2
	Anakinra	IL-1	Recombinant protein	Arthrofibrosis	Amgen/Biovitrum	Clinic^e
	CNTO-888	CCL2	Monoclonal antibody	IPF, fibrocyte reduction	Janssen	2
	Thalidomide	Anti-inflammatory, proapoptotic?	Small molecule	IPF	Celgene	2
	Azathioprine	Cytotoxic, immunosuppressive	Small molecule	IPF	Multiple	3
	Aviptadil	Vasoactive intestinal polypeptide analog	Synthetic peptide	Pulmonary arterial hypertension, IPF	mondoBIOTECH	1
Antioxidants	N-acetylcysteine	Oxidative stress	Small molecule	IPF, hepatic fibrosis	Multiple	3
Coagulation pathway	PAR1 antagonists	Thrombin and FXa signaling	Small molecule	IPF, hepatic fibrosis	Multiple	Preclinical
Others	Losartan	Angiotensin II receptor signaling	Small molecule	Hepatic, pulmonary and cardiac fibroses	Multiple	Clinic^f
	Bosentan	Dual endothelin receptor antagonism	Small molecule	Dermal fibrosis, IPF	Actelion	3

Approved for IPF in EU and Japan.

Approved for multiple myeloma.

Combination therapy with immunosuppressants.

Inhibits the receptor tyrosine kinases VEGFR, PDGFR and FGFR.

Approved for rheumatoid arthritis.

Approved for hypertension.

Several steps in cell growth, inflammation, and immune activation have become targets for antifibrotic intervention. Key targets that are now being tested in preclinical models or in phase 2 or phase 3 clinical trials are included.