| 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
Starting from a previously reported RORgamma inhibitor (1), successive efforts to improve in vivo potency were continued. Introduction of metabolically beneficial motifs in conjunction with scaffold hopping was examined, resulting in discovery of the second generation RORgamma inhibitor composed of a 4-(isoxazol-3-yl)butanoic acid scaffold (24). Compound 24 achieved a 10-fold improvement in in vivo potency in a mouse CD3 challenge model along with significant anti-inflammatory effects in a mouse dermatitis model.
Discovery of Second Generation RORgamma Inhibitors Composed of an Azole Scaffold.,Kotoku M, Maeba T, Fujioka S, Yokota M, Seki N, Ito K, Suwa Y, Ikenogami T, Hirata K, Hase Y, Katsuda Y, Miyagawa N, Arita K, Asahina K, Noguchi M, Nomura A, Doi S, Adachi T, Crowe P, Tao H, Thacher S, Hashimoto H, Suzuki T, Shiozaki M J Med Chem. 2019 Mar 1. doi: 10.1021/acs.jmedchem.8b01567. PMID:30776227[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kotoku M, Maeba T, Fujioka S, Yokota M, Seki N, Ito K, Suwa Y, Ikenogami T, Hirata K, Hase Y, Katsuda Y, Miyagawa N, Arita K, Asahina K, Noguchi M, Nomura A, Doi S, Adachi T, Crowe P, Tao H, Thacher S, Hashimoto H, Suzuki T, Shiozaki M. Discovery of Second Generation RORgamma Inhibitors Composed of an Azole Scaffold. J Med Chem. 2019 Mar 1. doi: 10.1021/acs.jmedchem.8b01567. PMID:30776227 doi:http://dx.doi.org/10.1021/acs.jmedchem.8b01567
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