VEGFR2 Kinase Inhibitor II

VEGFR-2-IN-44 (compound 4b) is a selective VEGF-R2 (Flk-1) inhibitor with an IC50 value of 70 nM. VEGFR-2-IN-44 also inhibits PDGF-Rβ with an IC50 of 920 nM[1].

A cell-permeable and reversible indolin-2-one class of receptor tyrosine kinase (RTK) inhibitor [IC₅₀ = 70 nM for VEGF-R2 (KDR/Flk-1), 920 nM for PDGF-Rβ, 4.92 μM for p60^c-src, and 13.3 μM for FGF-R1]. The inhibition is suggested to be competitive with respective to ATP. Also inhibits VEGF-induced (IC₅₀ = 110 nM) and PDGF-induced (IC₅₀ = 2.01 μM) cell proliferation in umbilical vein endothelial cells (HUVEC). Does not exhibit any inhibitory effect on EGF-R kinase activity (IC₅₀ >100 μM).

Cell permeable: yes

Flk-1: 70 nM (IC₅₀); PDGFR-β: 920 nM (IC₅₀)

[1] L Sun, et al. Identification of substituted 3-[(4,5,6, 7-tetrahydro-1H-indol-2-yl)methylene]-1,3-dihydroindol-2-ones as growth factor receptor inhibitors for VEGF-R2 (Flk-1/KDR), FGF-R1, and PDGF-Rbeta tyrosine kinases. J Med Chem. 2000 Jul 13;43(14):2655-63. DOI:10.1021/jm9906116