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

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.

• Författare: Anja Schäfer; Ethan S Burstein; Roger Olsson
• Avdelning/ar: Kemisk biologi med inriktning mot läkemedelsutveckling
• Publiceringsår: 2014
• Språk: Engelska
• Sidor: 1944-1947
• Publikation/Tidskrift/Serie: Bioorganic & Medicinal Chemistry Letters
• Volym: 24
• Issue: 8
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/24666648?dopt=Abstract; http://dx.doi.org/10.1016/j.bmcl.2014.03.003
• Dokumenttyp: Artikel i tidskrift
• Förlag: Elsevier
• Ämne: Pharmacology and Toxicology
• Status: Published
• Forskningsgrupp: Chemical Biology and Therapeutics
• ISBN/ISSN/Övrigt: ISSN: 0960-894X