Background:

SR1001 is a selective RORα and RORγ inverse agonist with Kis 172 and 111 nM, respectively.

SR1001 inhibits the development of murine TH17 cells by inhibition of IL-17A gene expression and protein production. SR1001 reduces the interaction of a coactivator TRAP220 NR box 2 peptide with RORγ in a dose dependent manner (IC50 value≈117 nM). Additionally, SR1001 inhibits the expression of cytokines when added to differentiated murine or human TH17 cells[1].

SR1001 effectively suppresses the clinical severity of autoimmune disease in mice. Administration of SR1001 to C57BL/6 mice suppresses the expression of hepatic ROR target genes, Cyp7b1, Rev-erbα, and Serpine 1[1]. SR1001 a RORα inverse agonist eliminats the circadian pattern of expression of citrate synthase mRNA in mice[2].

参考文献:
[1]. Solt LA, et al. Suppression of TH17 differentiation and autoimmunity by a synthetic ROR ligand. Nature. 2011 Apr 28;472(7344):491-4.
[2]. Crumbley C, et al. Regulation of expression of citrate synthase by the retinoic acid receptor-related orphan receptor α (RORα). PLoS One. 2012;7(4):e33804.