SB-267268

SB-267268 is a selective and nonpeptidic alpha (v)beta3 ( αvβ3 ) and alpha (v)beta5 ( αvβ5 ) integrins antagonist, with K i s 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 IC₅₀ s of 0.68 and 0.29 nM, respectively. SB-267268 reduces angiogenesis and VEGF expression ^[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].

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].

References:
[1]. Wilkinson-Berka JL, et al. SB-267268, a nonpeptidic antagonist of alpha(v)beta3 and alpha(v)beta5 integrins, reduces angiogenesis and VEGF expression in a mouse model of retinopathy of prematurity. Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1600-5.