WCF-598 (WCF598) is a potent, selective RXRγ PROTAC degrader with DC50 of 24.82 nM and 27.15 nM in 22Rv1 and VCaP-CRPC cells respectively.
WCF-598 exerts potent antiproliferative effects on VCaP-CRPC cells in a concentration-dependent manner, with an IC50 value of 88.46 nM.
WCF-598 displays a direct interaction to RXRγ with SPR KD of 234.2 nM.
WCF-598 demonstrates a favorable preference for degrading RXRγ over its closely related subtypes RXRα and RXRβ.
WCF-598 significantly induces degradation of AR-V7, with a DC50 of 122.0 nM and a Dmax of 63.26%, also effectively induces a reduction of the AR-V7 protein levels in a time-dependent manner in 22Rv1 cells.
The degradation of RXRγ protein induced by WCF-598 is mediated through the ubiquitin-proteasome pathway.
WCF-598 (100, 200, and 400 nM) potently induces cell apoptosis and ultimately suppresses the proliferation of 22Rv1 cells.
WCF-598 inhibits the progression of CRPC through several mechanisms, including the activation of the p53 signaling pathway, induction of apoptosis, enhancement of the DDR, inhibition of cell cycle progression and DNA replication.
WCF-598 (10 and 20 mg/kg, i.p.) resulted in significant and dose-dependent tumor suppression, achieving tumor growth inhibition (TGI) values of 45.46% (10 mg/kg) and 61.18% (20 mg/kg), respectively, induced the degradation of AR and AR-V7 protein in the tumor tissues.