Retinal pigment epithelium 65 (RPE65) also known as retinoid isomerohydrolase is a 65 kDa enzyme located within the human retinal pigment epithelium cells responsible for the chemical conversion of all-trans-retinyl ester to 11-cis-retinol in the visual cycle.

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Function

Structural Features of RPE65

Enzymatic Catalyzed Reaction

Protein-Ligand Interaction

Endogenous Ligand

Exogenous Ligand

(R)-Emixustat (ACU-4429)

(R)-emixustat (ACU-4429) is an investigational small molecule inhibitor of RPE65 first invented by a British-American chemist, Ian L. Scott. Formulated as an hydrochloride salt, (R)-emixustat hydrochloride is taken by mouth and functions as a visual cycle modulator (VCM) to reduce toxic retinal byproducts such as A2E.

In 2008, Acucela Inc. partnered with Otsuka Pharmaceutical Company for the continued development of (R)-emixustat as a potential inhibitor of RPE65. Currently (R)-emixustat is in Phase III clinical trials in the United States for the potential treatment of Stargard's disease, a juvenile form of atrophic (dry) age dependent macular degeneration (AMD). Additionally, (R)-emixustat is investigated as potential therapy for diabetic retinopathy and diabetic macular edema.

(S)-Emixustat

R/S Enantiomers Differences

Disease Implications

Medical Relevance

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