SB-267268

SB-267268 is a selective and nonpeptidic alpha(v)beta3 (αvβ3) and alpha(v)beta5 (αvβ5) integrins antagonist, with K_is of 0.9, 0.5 and 0.7 nM for human αvβ3, monkey αvβ3 and human αvβ5, respectively. SB-267268 inhibits human and mouse αvβ3 with IC₅₀s of 0.68 and 0.29 nM, respectively. SB-267268 reduces angiogenesis and VEGF expression^[1]. In Vitro: SB-267268 was much less potent for inhibition of human, mouse, and ratαvβ6 integrin. SB-267268 inhibits the attachment of bothαvβ3-transfected HEK293 cells to microtiter plate wells precoated with arginine-glycine-aspartic acid (RGD)-containing matrix proteins with IC₅₀ values of 12 nM. SB-267268 also inhibits vitronectin-mediated human and rat aortic smooth-muscle-cell (SMC) migration with IC₅₀ values of approximately 12.3 nM and 3.6 nM, respectively^[1]. In Vivo: SB-267268 (60 mg/kg; bi-daily, i.p.) reduces blood vessel profiles (BVPs) in the inner retina by 50%^[1].
In ROP mice treated with SB-267268, VEGF and VEGFR-2 gene expression in the inner nuclear layer (INL) and the ganglion cell layer (GCL) is reduced^[1].