Antibody drug conjugates of cleavable amino-benzoyl-maytansinoids
| Autor: | Carlos Hickey, Frank Delfino, Elizabeth Navarro, Thomas Nittoli, Shu Mao, Zhaoyuan Chen, Marcus Kelly, Arthur Kunz, Serena Carosso, Jessica R. Kirshner, Jing Shan, William C. Olson, Gavin Thurston, Markotan Thomas P, Nicholas J. Papadopoulos, Feng Zhao, Sosina Makonnen, Jan Spink |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Drug
Antibody-drug conjugate Immunoconjugates Cell Survival media_common.quotation_subject Clinical Biochemistry Cell Transplantation Heterologous Pharmaceutical Science Mice SCID Maytansinoid 01 natural sciences Biochemistry Cell Line chemistry.chemical_compound Structure-Activity Relationship Cell Line Tumor Neoplasms Drug Discovery medicine Animals Humans Maytansine Molecular Biology media_common Natural product biology 010405 organic chemistry Organic Chemistry Isotype Tubulin Modulators 0104 chemical sciences body regions 010404 medicinal & biomolecular chemistry medicine.anatomical_structure chemistry biology.protein Molecular Medicine Female Antibody Conjugate |
| Zdroj: | Bioorganicmedicinal chemistry. 28(23) |
| ISSN: | 1464-3391 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect