Meredith, Erik, Mainolfi, Nello, Poor, Stephen, Qiu, Yubin, Miranda, Karl, Powers, James, Liu, Donglei, Ma, Fupeng, Solovay, Catherine, Rao, Chang, Johnson, Leland, Ji, Nan, Artman Iii, Gerald, Hardegger, Leo, Elliott, Jason, Hanks, Shawn, Shen, Siyuan, Woolfenden, Amber, Zhang, Yiqin, Sivak, Jeremy, Long, Debby, Cepeda, Rosemarie, Hosagrahara, Vinayak, Lee, Wendy, Tarsa, Peter, Liu, Fang, Anderson, Karen and Jaffee, Bruce (2015) Discovery of Oral VEGFR-2 Inhibitors with Prolonged Ocular Retention that are Efficacious in Models of Wet Age-Related Macular Degeneration. Journal of Medicinal Chemistry.

Abstract

The benefit of intravitreal anti-VEGF therapy in treating wet age-related macular degeneration (AMD) has been well established. Identification of suitable VEGFR-2 inhibitors would provide alternative dosing opportunities beyond intravitreal injection. To identify such inhibitors, we employed a high–throughput in vivo screening strategy with a model of choroidal neovascularization and iterative compound design to provide VEGFR-2 inhibitors with potential to benefit wet AMD patients. These compounds, when dosed orally, provided good efficacy and preferential ocular tissue distribution while minimizing systemic exposure.

Item Type:	Article
Date Deposited:	28 Apr 2016 23:45
Last Modified:	28 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/27148