Download MendeleyDiscovery of substituted maleimides as liver x receptor agonists and determination of a ligand-bound crystal structure.
Jaye, M.C., Krawiec, J.A., Campobasso, N., Smallwood, A., Qiu, C., Lu, Q., Kerrigan, J.J., De Los Frailes Alvaro, M., Laffitte, B., Liu, W.S., Marino, J.P., Meyer, C.R., Nichols, J.A., Parks, D.J., Perez, P., Sarov-Blat, L., Seepersaud, S.D., Steplewski, K.M., Thompson, S.K., Wang, P., Watson, M.A., Webb, C.L., Haigh, D., Caravella, J.A., Macphee, C.H., Willson, T.M., Collins, J.L.(2005) J Med Chem 48: 5419-5422
- PubMed: 16107141
- DOI: https://doi.org/10.1021/jm050532w
- Primary Citation of Related Structures:
2ACL - 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.
Organizational Affiliation:
GlaxoSmithKline Research and Development, Research Triangle Park, North Carolina 27709, USA.
