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

Schäfer, Anja; Burstein, Ethan S and Olsson, Roger LU (2014) In Bioorganic & Medicinal Chemistry Letters 24(8). p.1944-1947
Abstract
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.
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Bioorganic & Medicinal Chemistry Letters
volume
24
issue
8
pages
1944 - 1947
publisher
Elsevier
external identifiers
  • pmid:24666648
  • wos:000333579500015
  • scopus:84897476143
ISSN
1090-2120
DOI
10.1016/j.bmcl.2014.03.003
language
English
LU publication?
yes
id
ed322deb-0754-4db5-91a0-423817822834 (old id 4379719)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24666648?dopt=Abstract
date added to LUP
2014-04-03 22:09:54
date last changed
2017-04-23 03:17:36
@article{ed322deb-0754-4db5-91a0-423817822834,
  abstract     = {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.},
  author       = {Schäfer, Anja and Burstein, Ethan S and Olsson, Roger},
  issn         = {1090-2120},
  language     = {eng},
  number       = {8},
  pages        = {1944--1947},
  publisher    = {Elsevier},
  series       = {Bioorganic & Medicinal Chemistry Letters},
  title        = {Bexarotene prodrugs: Targeting through cleavage by NQO1 (DT-diaphorase).},
  url          = {http://dx.doi.org/10.1016/j.bmcl.2014.03.003},
  volume       = {24},
  year         = {2014},
}