ABS-752

ABS-752 is a first-in-class **CRBN-modulating molecular glue degrader** currently in Phase 1 clinical trials for the treatment of hepatocellular carcinoma (HCC). It is a **prodrug** that is selectively activated by the monoamine oxidase **VAP-1** (vascular adhesion protein-1), which is highly overexpressed in inflamed and cirrhotic liver tissue. Upon activation by VAP-1, ABS-752 is converted to an aldehyde intermediate and subsequently to its active metabolite **ABT-002**. The active compound potently degrades two key protein targets: **GSPT1** (G1 to S phase transition 1) and **NEK7** (NIMA-related kinase 7), both CRBN neosubstrates. GSPT1 degradation is the primary mechanism of cytotoxicity with a DC50 of less than 1 nM, while NEK7 degradation contributes additional therapeutic benefits by shutting down the NLRP3 inflammasome pathway, reducing IL-1β in the tumor microenvironment. ABS-752 demonstrated exceptional efficacy in preclinical models, achieving complete tumor regression at 10 mg/kg twice daily in Hep3B xenograft models and showing tumor growth inhibition greater than 50% in four out of ten patient-derived xenograft models of HCC. Developed by **Captor Therapeutics**, ABS-752 exhibits a unique mechanism of tissue-selective activation, favorable safety profile in non-human primates, and no cytotoxicity in primary human hepatocytes.

Other names

CT-01CT01CT 01