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:
https://lup.lub.lu.se/record/4379719
- author
- Schäfer, Anja
; Burstein, Ethan S
and Olsson, Roger
LU
- organization
- publishing date
- 2014
- 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
- pmid:24666648
- scopus:84897476143
- ISSN
- 0960-894X
- 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
- 2016-04-01 10:48:32
- date last changed
- 2022-01-26 02:38:18
@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 = {{0960-894X}},
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}},
doi = {{10.1016/j.bmcl.2014.03.003}},
volume = {{24}},
year = {{2014}},
}