SB-267268, a nonpeptidic antagonist of αvβ 3 and αvβ5 integrins, reduces angiogenesis and VEGF expression in a mouse model of retinopathy of prematurity

Abstract

PURPOSE. To determine whether SB-267268, a nonpeptidic antagonist of the αvβ3 and αvβ5 integrins, attenuates angiogenesis in a murine model of retinopathy of prematurity (ROP) and alters the expression of vascular endothelial growth factor (VEGF) and its second receptor (VEGF-R2). METHODS. In receptor binding, SB-267268 exhibited nanomolar potency for human, monkey, and murine αvβ3 and αvβ5. SB-267268 inhibited the attachment of αvβ3- transfected HEK293 cells to microtiter plate wells precoated with RGD-containing matrix proteins, and vitronectin-mediated human and rat aortic smooth-muscle-cell migration. At postnatal day (P)12, C57BL/6 mice were exposed to 80% oxygen for 7 days followed by ..