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

M.C. Jaye, J.A. Krawiec, N. Campobasso, A. Smallwood, C.Y. Qiu, Q. Lu, J.J. Kerrigan, M.D.L. Alvaro, B. Laffitte, W.S. Liu, J.P. Marino, C.R. Meyer, J.A. Nichols, D.J. Parks, P. Perez, L. Sarov-Blat, S.D. Seepersaud, K.M. Steplewski, S.K. Thompson, P. WangM.A. Watson, C.L. Webb, David Haigh, J.A. Caravella, C.H. Macphee, T.M. Willson, J.L. Collins

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 (4) as an LXR ligand. 4 recruits the steroid receptor coactivator-1 to human LXR alpha and LXRP 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.
Original languageEnglish
Pages (from-to)5419-5422
Number of pages4
JournalJournal of Medicinal Chemistry
Volume48
Issue number17
DOIs
Publication statusPublished - 25 Aug 2005

ASJC Scopus subject areas

  • Organic Chemistry

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