1 results match your criteria: "Institut Claudius-Regaud-Institut Universitaire du Cancer Toulouse-Oncopole and UMR 1037 INSERM[Affiliation]"
Pharmaceuticals (Basel)
February 2021
Centre de Recherches en Cancérologie de Toulouse (CRCT), Institut Claudius-Regaud-Institut Universitaire du Cancer Toulouse-Oncopole and UMR 1037 INSERM, 31052 Toulouse, France.
The clinical use of cytotoxic agents is plagued by systemic toxicity. We report a novel approach that seeks to design a "combi-molecule" to behave as an alkylating agent on its own and to undergo acid-catalyzed conversion to two bioactive species at a pH range akin to that of a tumor microenvironment: an AL530 prototype was synthesized and we studied its ability to release a chlorambucil analogue (CBL-A) plus a potent mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor (PD98059) at different pHs in buffered solutions, plasma and tumors. Its potency was compared in vitro with CBL+PD98059 (SRB assay) and in vivo in a xenograft model.
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