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.
N-Acylthiadiazolines, a new class of liver X receptor agonists with selectivity for LXRbeta / V. Molteni, X. Li, J. Nabakka, F. Liang, J. Wityak, A. Koder, L. Vargas, R. Romeo, N. Mitro, P.A. Mak, H.M. Seidel, J.A Haslam, D. Chow, T. Tuntland, T.A. Spalding, A. Brock, M. Bradley, A. Castrillo, P. Tontonoz, E. Saez. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 50:17(2007 Aug 23), pp. 4255-4259.
N-Acylthiadiazolines, a new class of liver X receptor agonists with selectivity for LXRbeta
N. Mitro;
2007
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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