A5040190226- Retinal Diseases and Treatments
- Calcium signaling and nucleotide metabolism
- Neonatal Health and Biochemistry
- Retinal Development and Disorders
- Cellular transport and secretion
Case Western Reserve University
2021-2023
Recycling of all-trans-retinal to 11-cis-retinal through the visual cycle is a fundamental metabolic pathway in eye. A potent retinoid isomerase (RPE65) inhibitor, (R)-emixustat, has been developed and tested several clinical trials; however, it not received regulatory approval for use any specific retinopathy. Rapid clearance this drug presents challenges maintaining concentrations eyes within therapeutic window. To address pharmacokinetic inadequacy, we rationally designed synthesized...
In the eye, isomerization of all-trans-retinal to 11-cis-retinal is accomplished by a metabolic pathway termed visual cycle that critical for vision. RPE65 essential trans–cis isomerase this pathway. Emixustat, retinoid-mimetic inhibitor, was developed as therapeutic modulator and used treatment retinopathies. However, pharmacokinetic liabilities limit its further development including: (1) deamination γ-amino-α-aryl alcohol, which mediates targeted inhibition, (2) unwanted long-lasting...