4xt9
From Proteopedia
RORgamma (263-509) complexed with GSK2435341A and SRC2
Structural highlights
FunctionRORG_HUMAN Possible nuclear receptor for hydroxycholesterols, the binding of which strongly promotes coactivators recruitment. Essential for thymopoiesis and the development of several secondary lymphoid tissues, including lymph nodes. Involved in lineage specification of uncommitted CD4(+) T-helper cells into Th17 cells. Regulate the expression of several components of the circadian clock. Publication Abstract from PubMedA novel series of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as RORgammat inverse agonists was discovered. Binding mode analysis of a RORgammat partial agonist (2c) revealed by co-crystal structure in RORgammat LBD suggests that the inverse agonists do not directly interfere with the interaction between H12 and the RORgammat LBD. Detailed SAR exploration led to identification of potent RORgammat inverse agonists such as 3m with a pIC50 of 8.0. Selected compounds in the series showed reasonable activity in Th17 cell differentiation assay as well as low intrinsic clearance in mouse liver microsomes. Discovery of N-(4-aryl-5-aryloxy-thiazol-2-yl)-amides as potent RORgammat inverse agonists.,Wang Y, Yang T, Liu Q, Ma Y, Yang L, Zhou L, Xiang Z, Cheng Z, Lu S, Orband-Miller LA, Zhang W, Wu Q, Zhang K, Li Y, Xiang JN, Elliott JD, Leung S, Ren F, Lin X Bioorg Med Chem. 2015 Sep 1;23(17):5293-302. doi: 10.1016/j.bmc.2015.07.068. Epub, 2015 Aug 1. PMID:26277758[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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