αvβ6 Inhibitor

Bexotegrast (PLN-74809) is an orally active, potent dual αvβ6/αvβ1 integrin inhibitor with K_d of 5.7 nM and 3.4 nM, respectively. Bexotegrast inhibits αvβ6- and αvβ1-induced TGF-β activation with IC₅₀ values of 29.8 nM and 19.2 nM, respectively. Bexotegrast has antifibrogenic effects and block multiple avenues of TGF-β activation in the fibrotic lung.

A20FMDV2 is a highly selective αvβ6 integrin inhibitor with human IC₅₀ values of 3 nM and binds with at least 1000-fold selectivity over other RGD-binding integrins. A20FMDV2 binds to the integrin’s RGD-binding site, induces rapid integrin internalization, and delays post-internalization integrin recycling to the cell surface. A20FMDV2 can be used for the research of pancreatic cancer, breast cancer, colorectal cancer, ovarian cancer, oral squamous cell carcinoma.

STX-100 (BG00011) is a humanized monoclonal antibody targeting αVβ6 integrin. STX-100 specifically binds αVβ6 integrin, blocks latent TGF-β activation via latency-associated peptide (LAP) interaction prevention, and reduces profibrotic responses. STX-100 can be used for the research of idiopathic pulmonary fibrosis, and cancer.

EMD527040 is a potent and highly selective αvβ6 antagonist with antifibrotic activities. EMD527040 can be used for carcinoma and liver fibrosis research.

MORF-627 is a highly selective, orally active integrin αvβ6 inhibitor. By blocking TGF-β1 activation and pSMAD2 signaling, MORF-627 significantly reduces collagen deposition, epithelial-mesenchymal transition markers, and structural changes in fibrotic cells. MORF-627 exhibits significant antifibrotic efficacy without genotoxicity in idiopathic pulmonary fibrosis models. However, MORF-627 induces bladder epithelial proliferation and early invasive urothelial carcinoma in cynomolgus monkeys and human cells, and this toxic effect can be reversed by exogenous TGF-β. MORF-627 can be used for studying the pathological mechanisms of pulmonary fibrosis and evaluating drug safety.

αvβ6-IN-2 (compound 20) is a potent and orally active αvβ6 integrin inhibitor with a pIC₅₀ value of 7.8. αvβ6-IN-2 has the potential for the research of idiopathic pulmonary fibrosis.

αvβ6-IN-1 (compound 28) is a potent and orally active αvβ6 integrin inhibitor with a pIC₅₀ value of 8.1. αvβ6-IN-1 has the potential for the research of idiopathic pulmonary fibrosis.

αvβ6 integrin inhibitor 2 is a potent ανβ6 integrin inhibitor with an IC₅₀ of 96.5 nM (WO2020081154A1, example 19).