Basic Information
ID: ALA4033614
Journal: J Nat Prod
Title: Antineoplastic Agents. 603. Quinstatins: Exceptional Cancer Cell Growth Inhibitors.
Authors: Pettit GR, Melody N, Chapuis JC.
Abstract: Discovery of the exceptionally powerful anticancer drug dolastatin 10 (1), contained in the sea hare Dolabella auricularia, opened a new frontier needed for improving human cancer treatment. Subsequently, major advances have been achieved based on results of structurally modifying this unusual natural peptide while maintaining the remarkable anticancer activity necessary for preparation of successful monoclonal antibody drug conjugates (ADC). Among the first several hundred SAR products based on dolastatin 10 our group synthesized and termed auristatins was auristatin E (2a). An anticancer activity-equivalent, desmethylaurisatin E (2b), linked to a CD30 monoclonal antibody is the very successful anticancer drug Adcetris, now approved for use in 65 countries. In the present investigation, we discovered a new subset of auristatins designated quinstatins derived from dolastatin 10 by replacing the C-terminal Doe unit with a carefully designed quinoline, which led to low or subnanomolar levels of cancer cell growth inhibition required for construction of chemically unique ADC drugs. The synthesis of quinstatins 2-8 is presented along with their cancer cell line biological data.
CiteXplore: 28211277
DOI: 10.1021/acs.jnatprod.6b01006
Patent ID: ┄
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