XYD113 is a potent and highly selective, orally bioavailable CRBN-dependent GSPT1 molecular glue degrader, exerts potent antiproliferative activity against 22Rv1 cells with IC50 of 69 nM, induces complete degradation of GSPT1 at 111 nM.
XYD113 exhibits significant antiproliferative activity (IC50 < 100 nM) against multiple MYC-overexpressing cancer cell lines (22Rv1, MV4-11, MOLM-16, Calu-1, HS-SY-II), and induces GSPT1 degradation in a dose- and time-dependent manner.
XYD113 at 1 uM for 6 h led to a complete degradation of GSPT1 in 22Rv1 cells.
XYD113 shows exceptional selectivity over SALL4, IKZF1/2/3, ZFP91, or CK1α.
XYD113 functions as a molecular glue to facilitate the formation of the CRBN-GSPT1 ternary complex, a rate-limiting step in targeted protein degradation via the UPS.
XYD113 (5 mg/kg, oral) suppresses tumor growth in a 22Rv1 xenograft model with a favorable safety profile.