Issue 15, 2017, Issue in Progress

Pyridazinediones deliver potent, stable, targeted and efficacious antibody–drug conjugates (ADCs) with a controlled loading of 4 drugs per antibody

Abstract

Herein we report the use of pyridazinediones to functionalise the native solvent accessible interstrand disulfide bonds in trastuzumab with monomethyl auristatin E (MMAE). This method of conjugation delivers serum stable antibody–drug conjugates (ADCs) with a controlled drug loading of 4. Moreover, we demonstrate that the MMAE-bearing ADCs are potent, selective and efficacious against cancer cell lines in both in vitro and in vivo models.

Graphical abstract: Pyridazinediones deliver potent, stable, targeted and efficacious antibody–drug conjugates (ADCs) with a controlled loading of 4 drugs per antibody

Supplementary files

Article information

Article type
Paper
Submitted
18 Jan 2017
Accepted
19 Jan 2017
First published
30 Jan 2017
This article is Open Access
Creative Commons BY license

RSC Adv., 2017,7, 9073-9077

Pyridazinediones deliver potent, stable, targeted and efficacious antibody–drug conjugates (ADCs) with a controlled loading of 4 drugs per antibody

E. Robinson, J. P. M. Nunes, V. Vassileva, A. Maruani, J. C. F. Nogueira, M. E. B. Smith, R. B. Pedley, S. Caddick, J. R. Baker and V. Chudasama, RSC Adv., 2017, 7, 9073 DOI: 10.1039/C7RA00788D

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