Bexarotene prodrugs: Targeting through cleavage by NQO1 (DT-diaphorase).
Research output: Contribution to journal › Article
Bexarotene, a retinoid X receptor (RXR) agonist, is being tested as a potential disease modifying treatment for neurodegenerative conditions. To limit the peripheral exposure of bexarotene and release it only in the affected areas of the brain, we designed a prodrug strategy based on the enzyme NAD(P)H/quinone oxidoreductase (NQO1) that is elevated in neurodegenerative diseases. A series of indolequinones (known substrates of NQO1) was synthesized and coupled to bexarotene. Bexarotene-3-(hydroxymethyl)-5-methoxy-1,2-dimethyl-1H-indole-4,7-dione ester 7a was cleaved best by NQO1. The prodrugs are not cleaved by esterase.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Journal||Bioorganic & Medicinal Chemistry Letters|
|Publication status||Published - 2014|