ABS-752 hydrochloride is a prodrug of ABT-002 that could be activated by the monoamine oxidase VAP-1, ABS-752 is a molecular glue degrader of GSPT1 and NEK7 with DC50 of 1 nM and 9 nM in Hep3B cells (24 h, Dmax>95%).
ABS-752 does not form ternary complexes with CRBN and the neosubstrates. VAP-1, which is overexpressed in cirrhotic liver, is identified as the primary monoamine oxidase responsible for the conversion of ABS-752.
ABS-752 is potent against Hep3B and profoundly impacts viability in 575, HLE, JHH-7, HuH-7, SNU-423, SNU-878, and KKU-M213 cell lines.
ABS-752 degrades SALL4, NEK7, CK1α, and GSPT1, but not IKZF1 (unlike Pomalidomide in H929 cells).
EK7 and CK1α shows much weaker degradation after 6 h compared to GSPT1, with DC50 values of approximately 100 nM and >1000 nM, respectively.
ABT-002 as the active metabolite of ABS-752.
ABS-752 (100 mg/kg ABS-752 BID, PO) significant inhibited tumor growth in HCC PDX models.