title: Recent advances in the development of new auristatins: structural modifications and application in antibody drug conjugates.
abstract: Dolastatin 10 is a powerful antineoplastic agent and microtubule inhibitor that was discovered by Pettit et al. and published in 1987. Since then, many research groups have engaged in SAR studies of synthetic analogues, termed "auristatins". It was eventually discovered that auristatins are of great value as payloads in antibody drug conjugates (ADCs), which led to the FDA-approved ADC brentuximab vedotin (Seattle Genetics). Currently, over 30 ADCs in clinical trials employ auristatins as payloads, and there is a great interest in the research community, both on academic and industrial sides, to further study these analogues. This review will provide an overview of the recent advancements in auristatin development spanning a time frame of about the past ten years. The main focus will be to describe structural changes made to the auristatin peptide and their resulting biological activities in tumor cell proliferation assays. Selected ADC examples will also be described.
authors.affiliation: Pfizer Worldwide Research and Development, Worldwide Medicinal Chemistry, Oncology, Eastern Point Road, Groton, Connecticut 06340, United States.
authors.forename: Andreas
authors.initials: A
authors.lastname: Maderna
authors.affiliation: Pfizer Worldwide Research and Development, Worldwide Medicinal Chemistry, Oncology, Eastern Point Road, Groton, Connecticut 06340, United States.
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Leverett
mesh_terms: D062365:Aminobenzoates / Q000737:chemistry*; D000079963:Brentuximab Vedotin; D047630:Depsipeptides / Q000737:chemistry; D018796:Immunoconjugates / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*
chemical_list: D062365:Aminobenzoates; D047630:Depsipeptides; D018796:Immunoconjugates; D009842:Oligopeptides; C543533:auristatin; D000079963:Brentuximab Vedotin; C064570:dolastatin 10
keywords: antibody drug conjugates; auristatins; dolastatin 10; structural modifications