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

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Jaye MC, Krawiec JA, Campobasso N, Smallwood A, Qiu C, Lu Q, Kerrigan JJ, De Los Frailes Alvaro M, Laffitte B, Liu WS, Marino JP Jr, Meyer CR, Nichols JA, Parks DJ, Perez P, Sarov-Blat L, Seepersaud SD, Steplewski KM, Thompson SK, Wang P, Watson MA, Webb CL, Haigh D, Caravella JA, Macphee CH, Willson TM, Collins JL

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.

PubMed ID
16107141 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
1-BENZYL-3-(4-METHOXYPHENYLAMINO)-4-PHENYLPYRROLE-2,5-DIONEOxysterols receptor LXR-alphaEC 50 (nM)507.522Details
TO-901317Oxysterols receptor LXR-alphaEC 50 (nM)557.522Details