2. Academic Validation
  3. N-Acylthiadiazolines, a new class of liver X receptor agonists with selectivity for LXRbeta

N-Acylthiadiazolines, a new class of liver X receptor agonists with selectivity for LXRbeta

  • J Med Chem. 2007 Aug 23;50(17):4255-9. doi: 10.1021/jm070453f.
Valentina Molteni 1,  Xiaolin Li,  Juliet Nabakka,  Fang Liang,  John Wityak,  Alan Koder,  Leo Vargas,  Russell Romeo,  Nico Mitro,  Puiying A Mak,  H Martin Seidel,  Jennifer A Haslam,  Donald Chow,  Tove Tuntland,  Tracy A Spalding,  Ansgar Brock,  Michelle Bradley,  Antonio Castrillo,  Peter Tontonoz,  Enrique Saez
Affiliations

Affiliation

  • 1 Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, California 92121, USA. vmolteni@gnf.org
PMID: 17665897 DOI: 10.1021/jm070453f
Abstract

We have identified a novel liver X receptor (LXR) agonist (2) that activates the LXRbeta subtype with selectivity over LXRalpha. LXRbeta selectivity was confirmed using macrophages derived from LXR mutant mice. Despite its selectivity and modest potency, the compound can induce APO-AI-dependent Cholesterol efflux from macrophages with full efficacy. Our results indicate that it is possible to achieve significant LXRbeta selectivity in a small molecule while maintaining functional LXR activity.

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