Platelet-derived Growth Factor (PDGF) Inhibitor
In recent years, several RTK inhibitors with in vivo activity have been developed. Most of these inhibitors have focused on targeting the signaling pathways of VEGF, but diverse chemical compounds were also developed as selective PDGFR kinase inhibitors. Many of these PDGFR kinase inhibitors, including several quinoxalines were found to be highly potent and selective toward the PDGFR and its family members, kit and Flt3.
Inhibition of the PDGF signal pathway results in loss of pericytes and a reduction in vessel density in the neovascularized cornea that correlates with reduced expression of PDGF, ang1/2, and VEGF mRNA. PI3-K is known to be involved in the regulation of VEGF, ang1, and PDGF, as the PI3-K inhibitors wortmannin or LY294002 has similar effects. Since PDGF is a known stimulus for PI3-K activation, decrease in VEGF, ang1/2, and PDGF mRNA levels on administration of the PDGF inhibitor is caused by the decreased activation of the PI3-K signaling cascade.