A β-glucuronidase-responsive albumin-binding prodrug programmed for the double release of monomethyl auristatin E.

We report on the synthesis, in vitro and in vivo biological evaluations of a dimeric β-glucuronidase-responsive albumin-binding prodrug designed for the double release of MMAE upon a single enzymatic activation step. This prodrug produced a significant antitumour activity in mice bearing subcutaneous LS174T colorectal adenocarcinoma xenografts without inducing side effects.