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Liver X receptor modulators: a review of recently patented compounds (2007 - 2009)

Xiaolin Li1, Vince Yeh, Valentina Molteni

  • 1Genomics Institute of the Novartis Research Foundation, Department of Medicinal Chemistry, San Diego, CA 92121, USA.

Expert Opinion on Therapeutic Patents
|March 23, 2010
PubMed
Abstract

Insights

Liver X receptor (LXR) agonists show promise for atherosclerosis treatment by upregulating cholesterol transport genes. Future LXR agonists must avoid lipogenic effects, with selective LXRalpha activation being a key strategy.

Area of Science:

  • Molecular biology and pharmacology
  • Cardiovascular research
  • Drug discovery

Background:

  • Liver X receptors (LXRs) regulate cholesterol metabolism, glucose homeostasis, and inflammation.
  • LXRs play a crucial role in reverse cholesterol transport (RCT), making them a target for atherosclerosis treatment.
  • Previous LXR agonists demonstrated target engagement but raised safety concerns regarding lipogenesis.

Purpose of the Study:

  • To review patents and biological data of LXR agonists from 2006-2009.
  • To analyze structure-activity relationships and identify key players in LXR agonist development.
  • To explore therapeutic indications for LXR agonists, particularly in atherosclerosis.

Main Methods:

  • Comprehensive patent analysis of LXR agonists (late 2006-August 2009).
  • Review of chemical properties and biological data of selected LXR analogues.
  • Examination of therapeutic applications and structure-activity relationships.

Main Results:

  • Overview of major LXR scaffolds and their structure-activity relationships.
  • Identification of key companies involved in LXR agonist research.
  • Demonstration of LXR target gene upregulation (ABCA1, ABCG1) by an LXR agonist in vitro.

Conclusions:

  • The clinical success of LXR agonists hinges on developing agents that lack lipogenic side effects.
  • Selective activation of LXRalpha is a promising strategy to achieve therapeutic benefits while minimizing adverse effects.
  • Further research is needed to identify safe and effective LXR agonists for treating metabolic and cardiovascular diseases.

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