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

作者：Robinson Eifion; Nunes Joao P M; Vassileva Vessela; Maruani Antoine; Nogueira Joao C F; Smith Mark E B; Pedley R Barbara; Caddick Stephen; Baker James R; Chudasama Vijay

来源：RSC Advances, 2017, 7(15): 9073-9077.

DOI：10.1039/c7ra00788d

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.

• 出版日期2017