| 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
A high-throughput screen against Inventiva's compound library using a Gal4/RORgamma-LBD luciferase reporter gene assay led to the discovery of a new series of quinoline sulphonamides as RORgamma inhibitors, eventually giving rise to a lead compound having an interesting in vivo profile after oral administration. This lead was evaluated in a target engagement model in mouse, where it reduced IL-17 cytokine production after immune challenge. It also proved to be active in a multiple sclerosis model (EAE) where it reduced the disease score. The synthesis, structure activity relationship (SAR) and biological activity of these derivatives is described herein.
Discovery of novel quinoline sulphonamide derivatives as potent, selective and orally active RORgamma inverse agonists.,Amaudrut J, Argiriadi MA, Barth M, Breinlinger EC, Bressac D, Broqua P, Calderwood DJ, Chatar M, Cusack KP, Gauld SB, Jacquet S, Kamath RV, Kort ME, Lepais V, Luccarini JM, Masson P, Montalbetti C, Mounier L, Potin D, Poupardin O, Rouaud S, Spitzer L, Wallace CD Bioorg Med Chem Lett. 2019 May 9. pii: S0960-894X(19)30301-4. doi:, 10.1016/j.bmcl.2019.05.015. PMID:31101472[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Amaudrut J, Argiriadi MA, Barth M, Breinlinger EC, Bressac D, Broqua P, Calderwood DJ, Chatar M, Cusack KP, Gauld SB, Jacquet S, Kamath RV, Kort ME, Lepais V, Luccarini JM, Masson P, Montalbetti C, Mounier L, Potin D, Poupardin O, Rouaud S, Spitzer L, Wallace CD. Discovery of novel quinoline sulphonamide derivatives as potent, selective and orally active RORgamma inverse agonists. Bioorg Med Chem Lett. 2019 May 9. pii: S0960-894X(19)30301-4. doi:, 10.1016/j.bmcl.2019.05.015. PMID:31101472 doi:http://dx.doi.org/10.1016/j.bmcl.2019.05.015
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