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Bexarotene prodrugs: Targeting through cleavage by NQO1 (DT-diaphorase).

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Author

Summary, in English

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.

Publishing year

2014

Language

English

Pages

1944-1947

Publication/Series

Bioorganic & Medicinal Chemistry Letters

Volume

24

Issue

8

Document type

Journal article

Publisher

Elsevier

Topic

  • Pharmacology and Toxicology

Status

Published

Research group

  • Chemical Biology and Therapeutics

ISBN/ISSN/Other

  • ISSN: 0960-894X