In the latest issue of Communications Chemistry, part of the Nature Publishing Group portfolio, an article has been published presenting the research results of the Captor Therapeutics team on compound ABS-752, developed within the CT-01 project.
This candidate is currently in the clinical trial stage and may open an entirely new era in the treatment of hepatocellular carcinoma (HCC).

It is one of the first publications to demonstrate the practical application of molecular glue technology in the form of a prodrug, with significance that extends far beyond HCC itself.

ABS-752 stands out from existing therapies thanks to two key elements:

- Selective activation in tumor tissue:
The drug is activated by the enzyme VAP-1, whose levels are significantly elevated in the livers of patients with HCC and cirrhosis. This ensures that its action is concentrated within the tumor, reducing the risk of adverse effects.

- Dual mechanism of action:
At the same time, ABS-752 degrades two key proteins: GSPT1, responsible for tumor cell proliferation, and NEK7, an activator of the NLRP3 inflammasome. The combination of these mechanisms leads to both inhibition of tumor cell division and modulation of the inflammatory tumor microenvironment.

In preclinical studies, ABS-752 demonstrated highly promising results. In mouse models, at a dose of 10 mg/kg BID, complete regression of Hep3B tumors was achieved. In patient-derived xenograft (PDX) models of liver cancer, tumor growth inhibition was observed in 8 out of 10 cases, including 4 with inhibition above 50%. Importantly, in 28-day toxicology studies in primates, no severe adverse effects were observed, and in primary hepatocytes, ABS-752 showed no cytotoxicity.

ABS-752 is the first example of a molecular glue prodrug to enter clinical testing. The drug has already successfully passed preclinical evaluation and is now undergoing clinical trials. Thanks to its innovative approach, ABS-752 opens up new perspectives for more effective treatment of HCC and provides a blueprint for designing the next generation of selective protein degraders with improved safety profiles.

The article describes the discovery process of ABS-752, including prodrug optimization and the results of preclinical studies.

👉 https://www.nature.com/articles/s42004-025-01641-9

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