Nintedanib esylate

Nintedanib esylate (BIBF1120 esylate) is a potent triple angiokinase (VEGFR/PDGFR/FGFR) inhibitor with IC50 of 5/38/18/104/5 nM for VEGFR-2/FGFR-1/PDGFRα/VEGFR-1/VEGFR-3, respectively; inhibits MAPK and Akt signaling pathways, show inhibition of cell proliferation (EC50=10-80 nM) ; is fully efficacious in xenograft models and orally active.Lung Cancer Approved (In Vitro) :Nintedanib (BIBF 1120) binds to the ATP-binding site in the cleft between the amino and carboxy terminal lobes of the kinase domain. Nintedanib (BIBF 1120) inhibits proliferation of PDGF-BB stimulated BRPs with EC50 of 79 nM in cell assays. Nintedanib (BIBF 1120) (100 nM) blocks activation of MAPK after stimulation with 5% serum plus PDGF-BB. Nintedanib (BIBF 1120) prevents PDGF-BB stimulated proliferation with an EC50 of 69 nM in cultures of human vascular smooth muscle cells (HUASMC) . (In Vivo) :Nintedanib (BIBF 1120) (25-100 mg/kg daily p.o.) is highly active in all tumor models, including human tumor xenografts growing in nude mice and a syngeneic rat tumor model. This is evident in the magnetic resonance imaging of tumor perfusion after 3 days, reducing vessel density and vessel integrity after 5 days, and profound growth inhibition. Nintedanib (BIBF 1120) is orally available and displays encouraging efficacy in in vivo tumor models while being well tolerated.