Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 61, Issue 4, Pages 1622-1635Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.7b01731
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Funding
- Novartis Institute for Biomedical Research Pharmacokinetic Sciences group
- Novartis Institute for Biomedical Research Analytical Sciences group
- OPKD group of Alcon, a Novartis Company
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A noninvasive topical ocular therapy for the treatment of neovascular or wet age-related macular degeneration would provide a patient administered alternative to the current standard of care, which requires physician administered intravitreal injections. This manuscript describes a novel strategy for the use of in vivo models of choroidal neovascularization (CNV) as the primary means of developing SAP. related to efficacy from topical administration. Ultimately, this effort led to the discovery of acrizanib (LHA510), a small molecule VEGFR-2 inhibitor with potency and efficacy in rodent CNV models, limited systemic exposure after topical ocular administration, multiple formulation options, and an acceptable rabbit ocular PK profile.
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