Anti-GPC3 Antibody-drug Conjugate ZW251

**Semantic type:** Pharmacologic Substance

**Definition:** An antibody-drug conjugate (ADC) composed of a humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting the tumor-associated antigen glypican 3 (GPC3; GPC-3) conjugated, via a maleimide anchor and a glycyl glycyl phenylalanyl glycine (GGFG)-aminomethyl (AM) protease-cleavable linker, to the camptothecin-based topoisomerase 1 inhibitor (TOP1i) ZD06519, with potential antineoplastic activity. Upon administration of anti-GPC3 ADC ZW251, the antibody moiety targets and binds to GPC3 expressed on tumor cells. Upon binding, cellular uptake and linker cleavage, ZD06519 is released. ZD06519 inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and generating DNA single- and double-strand breaks. This leads to cell cycle arrest and tumor cell apoptosis. In addition, ADC ZW251 is able to induce a bystander effect on neighboring cells in the tumor environment. This further inhibits the proliferation of tumor cells. GPC3, a heparan sulfate proteoglycan and an oncofetal antigen protein, is overexpressed in a variety of cancers; it plays a role in cell division and growth regulation.

**Synonyms:** - ADC ZW251 - Anti-GPC3 ADC ZW251 - Anti-GPC3/TOP1i ADC ZW251 - Anti-GPC3/ZD06519 ADC ZW251 - Anti-Glypican 3 ADC ZW251 - ZW 251 - ZW-251 - ZW251