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ID: ALA4270644

Journal: Eur J Med Chem

Title: A β-glucuronidase-responsive albumin-binding prodrug for potential selective kinase inhibitor-based cancer chemotherapy.

Authors: Compain G, Oumata N, Clarhaut J, Péraudeau E, Renoux B, Galons H, Papot S.

Abstract: We report on the synthesis and in vitro biological evaluations of a nanomolar protein kinase inhibitor (PKI) and its β-glucuronidase-responsive albumin-binding prodrug. The highly potent PKI is 400-3400 times more cytotoxic than the well-known PKI Roscovitine. The prodrug is able to bind covalently to human serum albumin through Michael addition and release the cytotoxic PKI in the presence of β-glucuronidase, an enzyme over-expressed in the microenvironment of solid tumours.

CiteXplore: 30199702

DOI: 10.1016/j.ejmech.2018.08.100