duostatin

Duostatin refers to a family of cytotoxic anti-microtubule agents (payloads) that are used in antibody-drug conjugates (ADCs) for cancer therapy. These agents, including duostatin-3 and duostatin-5 (Duo-5), inhibit cell division by binding tubulin and disrupting microtubule polymerization, leading to mitotic arrest and cell death. They are structurally and functionally related to synthetic auristatin derivatives, but show unique pharmacology and cellular selectivity depending on their specific structure and linker. Duostatin payloads are not used alone as drugs, but as the cytotoxic component in ADCs, notably in A166 (with duostatin-5) for HER2-positive cancers and in preclinical or research-grade ADCs (such as trastuzumab-vc-duostatin-3). The payload is stably conjugated via enzymatically cleavable peptide linkers (often valine-citrulline), which are selectively cleaved in the lysosomes of targeted cancer cells, minimizing systemic toxicity[1][2][3][5].

Other names

duostatinduostatin-3duostatin3duostatin 3duostatin-5duostatin5duostatin 5duo-5duo5duo 5