Pyridazinediones deliver potent, stable, targeted and efficacious antibody–drug conjugates (ADCs) with a controlled loading of 4 drugs per antibody. Issue 15 (30th January 2017)

• Record Type: Journal Article
• Authors: Robinson, Eifion; Nunes, João P. M.; Vassileva, Vessela; Maruani, Antoine; Nogueira, João C. F.; Smith, Mark E. B.; Pedley, R. Barbara; Caddick, Stephen; Baker, James R.; Chudasama, Vijay
• Is Part Of: RSC advances. Volume 7:Issue 15(2017)
• Page Start: 9073
• Page End: 9077
• Publication Date: 2017-01-30
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7ra00788d
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Delivering potent, stable, targeted and in vivo efficacious antibody–drug conjugates (ADCs) using pyridazinedione functional disulfide re-bridging reagents. 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.