Structural highlights
Function
[RORG_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 PubMed
RORgamma plays a critical role in controlling a pro-inflammatory gene expression program in several lymphocyte lineages including T cells, gammadelta T cells, and innate lymphoid cells. RORgamma-mediated inflammation has been linked to susceptibility to Crohn's disease, arthritis, and psoriasis. Thus inverse agonists of RORgamma have the potential of modulating inflammation. Our goal was to optimize two RORgamma inverse agonists: T0901317 from literature and 1 that we obtained from internal screening. We used information from internal X-ray structures to design two libraries that led to a new biaryl series.
Discovery of biaryls as RORgamma inverse agonists by using structure-based design.,Enyedy IJ, Powell NA, Caravella J, van Vloten K, Chao J, Banerjee D, Marcotte D, Silvian L, McKenzie A, Hong VS, Fontenot JD Bioorg Med Chem Lett. 2016 Apr 1. pii: S0960-894X(16)30341-9. doi:, 10.1016/j.bmcl.2016.03.109. PMID:27080181[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Enyedy IJ, Powell NA, Caravella J, van Vloten K, Chao J, Banerjee D, Marcotte D, Silvian L, McKenzie A, Hong VS, Fontenot JD. Discovery of biaryls as RORgamma inverse agonists by using structure-based design. Bioorg Med Chem Lett. 2016 Apr 1. pii: S0960-894X(16)30341-9. doi:, 10.1016/j.bmcl.2016.03.109. PMID:27080181 doi:http://dx.doi.org/10.1016/j.bmcl.2016.03.109
