1. Discovery of Oral VEGFR-2 Inhibitors with Prolonged Ocular Retention That Are Efficacious in Models of Wet Age-Related Macular Degeneration.
- Author
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Meredith, Erik L., Mainolfi, Nello, Poor, Stephen, Yubin Qiu, Miranda, Karl, Powers, James, Donglei Liu, Fupeng Ma, Solovay, Catherine, Chang Rao, Johnson, Leland, Nan Ji, Artman, Gerald, Hardegger, Leo, Shawn Hanks, Siyuan Shen, Woolfenden, Amber, Fassbender, Elizabeth, Sivak, Jeremy M., and Yiqin Zhang
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VASCULAR endothelial growth factor receptors , *RETINAL degeneration treatment , *DUANE retraction syndrome , *ORAL medication , *NEOVASCULARIZATION ,AGE factors in retinal degeneration - Abstract
The benefit of intravitreal anti-VEGF therapy in treating wet age-related macular degeneration (AMD) is well established. Identification of VEGFR-2 inhibitors with optimal ADME properties for an ocular indication provides opportunities for dosing routes beyond intravitreal injection. We employed a high-throughput in vivo screening strategy with rodent models of choroidal neovascularization and iterative compound design to identify VEGFR-2 inhibitors with potential to benefit wet AMD patients. These compounds demonstrate preferential ocular tissue distribution and efficacy after oral administration while minimizing systemic exposure. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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