Antibody drug conjugates of cleavable amino-alkyl and aryl maytansinoids

Autor:	Jing Shan, Feng Zhao, Xiaobo Jiang, Sosina Makonnen, Nicholas J. Papadopoulos, John S. Rudge, Donna Hylton, Elizabeth Navarro, Thomas Nittoli, Michele Tait, Jessica R. Kirshner, Markotan Thomas P, Zhaoyuan Chen, Kathleen Provoncha, Carlos Hickey, Arthur Kunz, Jason T. Giurleo, Jan Spink, Gavin Thurston, Frank Delfino, Marcus Kelly
Rok vydání:	2017
Předmět:	0301 basic medicine Drug Male Antibody-drug conjugate media_common.quotation_subject Clinical Biochemistry Pharmaceutical Science Antineoplastic Agents CHO Cells Maytansinoid Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Cricetulus Immunotoxin Cell Line Tumor Drug Discovery Animals Humans Maytansine Molecular Biology media_common Natural product biology Immunotoxins Organic Chemistry Antibodies Monoclonal Small molecule Xenograft Model Antitumor Assays body regions ErbB Receptors Kinetics 030104 developmental biology chemistry 030220 oncology & carcinogenesis Cancer research biology.protein Molecular Medicine Female Antibody Hydrophobic and Hydrophilic Interactions Conjugate
Zdroj:	Bioorganicmedicinal chemistry. 26(9)
ISSN:	1464-3391
Popis:	Natural products have been used for many medicinal purposes for centuries. Antibody drug conjugates (ADCs) have utilized this rich source of small molecule therapeutics to produce several clinically useful treatments. ADCs based on the natural product maytansine have been successful clinically. The authors further the utility of the anti-cancer natural product maytansine by developing efficacious payloads and linker-payloads for conjugating to antibodies. The success of our approach was realized in the EGFRvIII targeting ADC EGFRvIII-16. The ADC was able to regress tumors in 2 tumor models (U251/EGFRvIII and MMT/EGFRvIII). When compared to a positive control ADC, the efficacy observed was similar or improved while the isotype control ADCs had no effect.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dbd038dc1328967ccf7495a2b9161a1d https://pubmed.ncbi.nlm.nih.gov/29605304 Zobrazit plný text záznamu Full Text from ScienceDirect