W6134，5MG，SML4137-5MG，Sigma

Biochem/physiol Actions

Cell penetrant, highly potent, selective, and non-toxic RORγ covalent inhibitor.

W6134 is a highly potent, selective RORγ (retinoic acid receptor-related orphan receptor γ) armed with a cell-permeable acrylamide warhead, which specifically targets RORγ (IC50 = 210 nM in HEK293Tcells co-transfected with Gal4-RORγ-LBD) by covalently modifying RORγ-Cys320 thiol while showing minimal activity against other nuclear receptors such as RORα, RXRγ, and ERRγ (IC50 > 20 μM). W6134 is effective in inducing apoptosis in C4-2B and 22Rv1 cell lines and reduces RORγ-mediated transcription, leading to decreased androgen receptor (AR) expression in a dose- and time-dependent manner. When tested in vivo (T1/2 = 21.3 min in mouse liver microsomes), W6134 significantly suppresses tumor growth in castration-resistant prostate cancers (CRPC) xenograft mouse models (5 or 10 mg/kg, i.p.) demonstrating its efficacy and safety.