| References: |
CWHM-12 a novel small molecule inhibitor of αV integrins with IC50s of 1.8/0.8/1.5/0.2 nM for αvβ1/αvβ3/αvβ8; less potency on αvβ5(IC50=61 nM) and on inhibition on αIIbβ3/α2β1/α10β1.in vitro: CWHM 12 demonstrated 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.
in vivo: Treated mice with CCl4 for 3 weeks to establish fibrotic disease and then treated with CWHM 12 or vehicle for the final 3 weeks of CCl4. CWHM12 significantly reduced liver fibrosis even after fibrotic disease had been established. Similar to our findings in the liver, administration of CWHM 12 significantly inhibited progression of pulmonary fibrosis. |
