A2-tub

**A2-tub** is a preclinical Glypican-3-targeted Adnectin-drug conjugate developed by Bristol Myers Squibb for hepatocellular carcinoma. It consists of the engineered 10th fibronectin type III domain Adnectin A2, which binds human and murine Glypican-3, site-specifically conjugated through an engineered cysteine to a cytotoxic tubulysin analog at a drug-to-Adnectin ratio of one. The Adnectin directs tumor-cell localization through Glypican-3 binding, while the tubulysin payload inhibits tubulin polymerization and disrupts microtubule function, producing antimitotic cytotoxicity. In mouse Hep3B xenograft models, A2-tub showed tumor localization, rapid systemic clearance, and antitumor activity. ([ncbi.nlm.nih.gov](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158766/))