2. Academic Validation
  3. Discovery of substituted maleimides as liver X receptor agonists and determination of a ligand-bound crystal structure

Discovery of substituted maleimides as liver X receptor agonists and determination of a ligand-bound crystal structure

  • J Med Chem. 2005 Aug 25;48(17):5419-22. doi: 10.1021/jm050532w.
Michael C Jaye 1,  John A Krawiec,  Nino Campobasso,  Angela Smallwood,  Chunyan Qiu,  Quinn Lu,  John J Kerrigan,  Maite De Los Frailes Alvaro,  Bryan Laffitte,  Wu-Schyong Liu,  Joseph P Marino Jr,  Craig R Meyer,  Jason A Nichols,  Derek J Parks,  Paloma Perez,  Lea Sarov-Blat,  Sheila D Seepersaud,  Klaudia M Steplewski,  Scott K Thompson,  Ping Wang,  Mike A Watson,  Christine L Webb,  David Haigh,  Justin A Caravella,  Colin H Macphee,  Timothy M Willson,  Jon L Collins
Affiliations

Affiliation

  • 1 GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA.
PMID: 16107141 DOI: 10.1021/jm050532w
Abstract

Substituted 3-(phenylamino)-1H-pyrrole-2,5-diones were identified from a high throughput screen as inducers of human ATP binding cassette transporter A1 expression. Mechanism of action studies led to the identification of GSK3987 as an LXR ligand. GSK3987 recruits the steroid receptor coactivator-1 to human LXRalpha and LXRbeta with EC(50)s of 40 nM, profiles as an LXR Agonist in functional assays, and activates LXR though a mechanism that is similar to first generation LXR agonists.

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