SKLB1002 is a potent inhibitor of VEGF receptor 2 with IC50 value of 32 nM [1].
VEGF receptor 2 (VEGFR2) is a major receptor for vascular endothelial growth factor (VEGF) and plays an important role in angiogenesis and VEGF-stimulated proliferation, migration, and sprouting of cultured endothelial cells [1].
SKLB1002 is a potent VEGFR2 inhibitor. In human umbilical vein endothelial cells (HUVEC), SKLB1002 significantly inhibited VEGF-induced HUVEC proliferation with IC50 value of 11.9 μM. Also, SKLB1002 inhibited HUVEC migration, invasion and tube formation in a dose-dependent way. SKLB1002 (10 μM) significantly inhibited VEGF-induced phosphorylation of VEGFR2, ERK, Src and FAK [1].
In zebrafish embryos, SKLB1002 (2.5 μM) significantly inhibited the growth of intersegmental vessels. In mice bearing SW620 or HepG2 xenografts, SKLB1002 (100 mg/kg) significantly inhibited tumor volume and inhibited tumor growth by 60%. Also, SKLB1002 reduced the microvessel density [1]. In mice with 4T1 tumor, SKLB1002 significantly reduced the tumor vessel density [2].
References:
[1]. Zhang S, Cao Z, Tian H, et al. SKLB1002, a novel potent inhibitor of VEGF receptor 2 signaling, inhibits angiogenesis and tumor growth in vivo. Clin Cancer Res, 2011, 17(13): 4439-4450.
[2]. Shen G, Li Y, Du T, et al. SKLB1002, a novel inhibitor of VEGF receptor 2 signaling, induces vascular normalization to improve systemically administered chemotherapy efficacy. Neoplasma, 2012, 59(5): 486-493.