Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 58, Issue 23, Pages 9273-9286Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.5b01227
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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.
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