CWHM-12

CWHM-12 is a potent inhibitor of αV integrins with IC₅₀s of 0.2, 0.8, 1.5, and 1.8 nM for αvβ8, αvβ3, αvβ6, and αvβ1. IC50 & Target:IC50: 0.2 nM (αvβ8), 0.8 nM (αvβ3), 1.5 nM (αvβ6), 1.8 nM (αvβ1), 61 nM (αvβ5)^[1] In Vitro: CWHM-12 (CWHM 12) also less potently inhibits αvβ5 (IC₅₀=61 nM) and αIIbβ3/α2β1/α10β1 (IC₅₀>5000 nM). CWHM-12 demonstrates high potency against all of the five possible β subunit binding partners (αvβ1, αvβ3, αvβ5, αvβ6 and αvβ8) in in vitro ligand-binding assays, with somewhat less potency against αvβ5 than against the other αv integrins^[1]. In Vivo: Mice are treated with CCl₄ for 3 weeks to establish fibrotic disease and then treated with CWHM-12 (CWHM 12) or vehicle for the final 3 weeks of CCl₄. CWHM-12 significantly reduces liver fibrosis even after fibrotic disease have been established. Digital image quantitation demonstrates significantly reduced p-SMAD3 signaling in the livers of CWHM-12 treated mice compare to controls, demonstrating that the protection from CCl₄-induced hepatic fibrosis observed in CWHM-12 treated mice is due at least in part to a reduction in TGF-β activation by αv integrins. Besides, administration of CWHM-12 significantly inhibited progression of pulmonary fibrosis^[1].