Tag: dolastatin 10

Synthesis and evaluation of novel dolastatin 10 derivatives for versatile conjugations

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http://redrooktattoo.com/tinfm.php Dolastatin 10 ( 1) is a highly potent cytotoxic microtubule inhibitor (cytotoxicity IC50 < 5.0 nM) and several of its analogs have recently been used as payloads in antibody drug conjugates. Herein, we describe the design and synthesis of a series of novel dolastatin 10 analogs useful as payloads for conjugated drugs. We explored analogs containing functional groups at the thiazole moiety at the C-terminal of dolastatin 10. The functional groups included amines, alcohols, and thiols, which are representative structures used in known conjugated drugs. These novel analogs showed excellent potency in a tumor cell proliferation assay, and thus this series of dolastatin 10 analogs is suitable as versatile payloads in conjugated drugs. Insights into the structure–activity relationships of the analogs are also discussed.(Bioorganic & Medicinal Chemistry. Volume 26, Issue 8, 1 May 2018, Pages 1643-1652.)