SR 2211 is a potent and selective inverse agonist of RORγ with IC50 value of 320 nM .
RAR-related orphan receptor gamma (RORγ) is a nuclear receptor and a DNA-binding transcription factor. RORγ plays an important role in the regulation of circadian rhythms and Th17 cell differentiation .
SR 2211 is a potent and selective RORγ inverse agonist. SR2211 bound to RORγ with Ki value of 105 nM. SR2211 (10 μM) inhibited RORγ activity by 90% but didn’t affect the transcriptional activity of RORα and farnesoid X receptors (FXR). SR2211 showed weak activation of liver X receptor α (LXRα). In EL-4 murine T lymphocyte cell line, SR2211 (5 μM) followed by PMA/ionomycin significantly inhibited the expression of IL-17 and IL-23 receptor in a dose-dependent way . Enriched naive CD4+ T cells under Th17 polarizing conditions, SR2211 significantly inhibited the production of IL-17, which suggested that SR2211 inhibited Th17 cell differentiation. In LPS-stimulated RAW 264.7 cells, SR2211 (5 μM) inhibited the expression of TNFα, IL-1β and IL-6, the proinflammatory cytokines that played an important role in the pathogenesis of RA .
Of the CIA mouse model, SR2211 (20 mg/kg) inhibited the development of arthritis in a dose-dependent way .
. Kumar N, Lyda B, Chang MR, et al. Identification of SR2211: a potent synthetic RORγ-selective modulator. ACS Chem Biol, 2012, 7(4): 672-677.
. Chang MR, Lyda B, Kamenecka TM, et al. Pharmacologic Repression of Retinoic Acid Receptor-Related Orphan Nuclear Receptor γ Is Therapeutic in the Collagen-Induced Arthritis Experimental Model. Arthritis Rheumatol, 2014, 66(3): 579-588.
|Physical Appearance||A crystalline solid|
|Storage||Store at -20°C|
|Solubility||Soluble in DMSO|
|Shipping Condition||Evaluation sample solution : ship with blue ice.All other available size: ship with RT , or blue ice upon request|
|General tips||For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.|