Ethanone, 1-[4-[[4'-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl][1,1'-biphenyl]-4-yl]methyl]-1-piperazinyl]-, hydrochloride (1:1)

Description

Retinoic acid receptor-related nuclear receptor γ (RORγ) plays a central role in T cell differentiation, particularly in the development of T_H17 cells, which are implicated in autoimmune diseases like multiple sclerosis and rheumatoid arthritis.^1,2 SR 1555 is a selective ligand of RORγ (IC₅₀ = 1 μM).³ It does not bind RORα, LXR, or FXR. SR 1555 acts as an inverse agonist of RORγ, inhibiting endogenous IL-17A gene expression in mouse splenocytes and suppressing differentiation of T_H17 cells when cultured under T_H17 polarizing conditions.³ Moreover, SR 1555 stimulates T regulatory development when cultured under T regulatory polarizing conditions, unlike digoxin and ursolic acid.³

References

1. Ivanov, I.I., McKenzie, B.S., Zhou, L., et al. The orphan nuclear receptor RORγt directs the differentiation program of proinflammatory IL-17+ T helper cells Cell 126(6),1121-1133(2006).
2. Solt, L.A., Kumar, N., Nuhant, P., et al. Suppression of T_H17 differentiation and autoimmunity by a synthetic ROR ligand Nature 472(7344),491-494(2011).
3. Solt, L.A., Kumar, N., He, Y., et al. Identification of a selective RORγ ligand that suppresses T_H17 cells and stimulates T regulatory cells ACS Chem. Biol. 7,1515-1519(2012).