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Bioorg Med Chem ; 28(23): 115785, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33099182

RESUMO

ADCs based on the natural product maytansine have been successfully employed clinically. In a previous report, ADCs based on hydrophilic non-cell permeable maytansinoids was presented. The authors in this report further explore the maytansine scaffold to develop tubulin inhibitors capable of cell permeation. The research resulted in amino-benzoyl-maytansinoid payloads that were further elaborated with linkers for conjugating to antibodies. This approach was applied to MUC16 tumor targeting antibodies for ovarian cancers. A positive control ADC was evaluated alongside the amino-benzoyl-maytansinoid ADC and the efficacy observed was equivalent while the isotype control ADCs had no effect.


Assuntos
Imunoconjugados/metabolismo , Maitansina/química , Moduladores de Tubulina/química , Animais , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Imunoconjugados/química , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Maitansina/metabolismo , Camundongos SCID , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Relação Estrutura-Atividade , Transplante Heterólogo , Moduladores de Tubulina/metabolismo
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