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Identification of novel subtype selective RAR agonists

Piu, Fabrice ; Gauthier, Natalie K. ; Olsson, Roger LU ; Currier, Erika A. ; Lund, Birgitte W. ; Croston, Glenn E. ; Hacksell, Uli and Brann, Mark R. (2005) In Biochemical Pharmacology 71(1-2). p.156-162
Abstract

Drugs targeting retinoid receptors have been developed to treat a variety of therapeutic indications, but their success has been limited in part due to lack of selectivity. A novel functional cell-based assay R-SAT™ was employed to screen a small molecule chemical library and identify a variety of novel RAR agonists with various subtype selectivities, including RARβ/γ and RARγ selective agonists. A novel class of synthetic compounds that distinguishes between the different RARβ isoforms is described. This pharmacophore displays anti-proliferative activity and induces differentiation in a neuronal cell line, consistent with a classical retinoid mechanism of action while providing unique subtype selectivity. These novel subtype selective... (More)

Drugs targeting retinoid receptors have been developed to treat a variety of therapeutic indications, but their success has been limited in part due to lack of selectivity. A novel functional cell-based assay R-SAT™ was employed to screen a small molecule chemical library and identify a variety of novel RAR agonists with various subtype selectivities, including RARβ/γ and RARγ selective agonists. A novel class of synthetic compounds that distinguishes between the different RARβ isoforms is described. This pharmacophore displays anti-proliferative activity and induces differentiation in a neuronal cell line, consistent with a classical retinoid mechanism of action while providing unique subtype selectivity. These novel subtype selective RAR agonists could serve as powerful tools to probe into subtype and isoform-specific retinoid function.

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author
; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
in
Biochemical Pharmacology
volume
71
issue
1-2
pages
156 - 162
publisher
Elsevier
external identifiers
  • pmid:16303118
  • scopus:28244470800
ISSN
0006-2952
DOI
10.1016/j.bcp.2005.10.025
language
English
LU publication?
no
id
211db813-26aa-48e8-abd3-4737c67d0af9
date added to LUP
2019-10-02 10:31:48
date last changed
2020-01-13 02:26:11
@article{211db813-26aa-48e8-abd3-4737c67d0af9,
  abstract     = {<p>Drugs targeting retinoid receptors have been developed to treat a variety of therapeutic indications, but their success has been limited in part due to lack of selectivity. A novel functional cell-based assay R-SAT™ was employed to screen a small molecule chemical library and identify a variety of novel RAR agonists with various subtype selectivities, including RARβ/γ and RARγ selective agonists. A novel class of synthetic compounds that distinguishes between the different RARβ isoforms is described. This pharmacophore displays anti-proliferative activity and induces differentiation in a neuronal cell line, consistent with a classical retinoid mechanism of action while providing unique subtype selectivity. These novel subtype selective RAR agonists could serve as powerful tools to probe into subtype and isoform-specific retinoid function.</p>},
  author       = {Piu, Fabrice and Gauthier, Natalie K. and Olsson, Roger and Currier, Erika A. and Lund, Birgitte W. and Croston, Glenn E. and Hacksell, Uli and Brann, Mark R.},
  issn         = {0006-2952},
  language     = {eng},
  month        = {12},
  number       = {1-2},
  pages        = {156--162},
  publisher    = {Elsevier},
  series       = {Biochemical Pharmacology},
  title        = {Identification of novel subtype selective RAR agonists},
  url          = {http://dx.doi.org/10.1016/j.bcp.2005.10.025},
  doi          = {10.1016/j.bcp.2005.10.025},
  volume       = {71},
  year         = {2005},
}