auristatin T

Auristatin T is a potent, membrane-impermeable microtubule inhibitor developed by Seagen (formerly Seattle Genetics) for use as a cytotoxic payload in antibody-drug conjugates (ADCs). As a synthetic analog of dolastatin 10, it binds to tubulin, disrupting microtubule dynamics and inducing cell cycle arrest and apoptosis in rapidly dividing cancer cells. Its membrane-impermeable nature is a key differentiator from other auristatin payloads like monomethyl auristatin E (MMAE), as it is designed to minimize the bystander effect—the killing of neighboring cells that do not express the target antigen—thereby potentially improving the therapeutic window and reducing off-target systemic toxicity. Preclinical research has explored its application in ADCs targeting various markers, such as CD317, for the treatment of hematological malignancies including acute myeloid leukemia (AML).