| Structural highlights
Function
[NR1H2_HUMAN] Orphan receptor. Binds preferentially to double-stranded oligonucleotide direct repeats having the consensus half-site sequence 5'-AGGTCA-3' and 4-nt spacing (DR-4). Regulates cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8 (By similarity). [RXRB_HUMAN] Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Specifically binds 9-cis retinoic acid (9C-RA).
Publication Abstract from PubMed
Liver X receptor (LXR) agonists have been reported to lower brain amyloid beta (Abeta) and thus to have potential for the treatment of Alzheimer's disease. Structure and property based design led to the discovery of a series of orally bioavailable, brain penetrant LXR agonists. Oral administration of compound 18 to rats resulted in significant upregulation of the expression of the LXR target gene ABCA1 in brain tissue, but no significant effect on Abeta levels was detected.
Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core.,Tice CM, Noto PB, Fan KY, Zhao W, Lotesta SD, Dong C, Marcus AP, Zheng YJ, Chen G, Wu Z, Van Orden R, Zhou J, Bukhtiyarov Y, Zhao Y, Lipinski K, Howard L, Guo J, Kandpal G, Meng S, Hardy A, Krosky P, Gregg RE, Leftheris K, McKeever BM, Singh SB, Lala D, McGeehan GM, Zhuang L, Claremon DA Bioorg Med Chem Lett. 2016 Aug 29. pii: S0960-894X(16)30921-0. doi:, 10.1016/j.bmcl.2016.08.089. PMID:27599745[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tice CM, Noto PB, Fan KY, Zhao W, Lotesta SD, Dong C, Marcus AP, Zheng YJ, Chen G, Wu Z, Van Orden R, Zhou J, Bukhtiyarov Y, Zhao Y, Lipinski K, Howard L, Guo J, Kandpal G, Meng S, Hardy A, Krosky P, Gregg RE, Leftheris K, McKeever BM, Singh SB, Lala D, McGeehan GM, Zhuang L, Claremon DA. Brain penetrant liver X receptor (LXR) modulators based on a 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole core. Bioorg Med Chem Lett. 2016 Aug 29. pii: S0960-894X(16)30921-0. doi:, 10.1016/j.bmcl.2016.08.089. PMID:27599745 doi:http://dx.doi.org/10.1016/j.bmcl.2016.08.089
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