SR1001 is a selective ROR and ROR inverse agonist; suppresses TH17 cell differentiation and inhibits autoimmunity.
SR1001 binds specifically to the ligand-binding domains of ROR and RORt, inducing a conformational change within the ligand-binding domain that encompasses the repositioning of helix 12 and leads to diminished affinity for co-activators and increased affinity for co-repressors, resulting in suppression of the receptors' transcriptional activity. SR1001 inhibited the development of murine T(H)17 cells, as demonstrated by inhibition of interleukin-17A gene expression and protein production. Furthermore, SR1001 inhibited the expression of cytokines when added to differentiated murine or human T(H)17 cells . SR1001 reduced the interaction of a coactivator TRAP220 NR box 2 peptide with ROR in a dose dependent manner(IC50=117 nM) .