tcsc3475 Nintedanib esylate

Nintedanib esylate (BIBF 1120 esylate) is a potent triple angiokinase inhibitor for VEGFR1/2/3, FGFR1/2/3 and PDGFRα/β with IC₅₀s of 34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM and 59 nM/65 nM, respectively.

IC50 & Target: IC50: 34 nM (VEGFR1), 13 nM (VEGFR2), 13 nM (VEGFR3), 69 nM (FGFR1), 37 nM (FGFR1), 108 nM (FGFR1), 59 nM (PDGFRα), 65 nM (PDGFRβ)^[1]

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)^[1].

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^[1]. Nintedanib (BIBF 1120) is orally available and displays encouraging efficacy in in vivo tumor models while being well tolerated^[2].