title: Discovery of a new class of catalytic topoisomerase II inhibitors targeting the ATP-binding site by structure based design. Part I.
abstract: Topoisomerase II is a validated target in oncology. Among the different ways of blocking the function of this enzyme, inhibiting its ATPase activity has been relatively less investigated. In an effort to identify topoisomerase II inhibitors of a novel type, exerting their action by this mechanism, we have designed a purine inhibitor scaffold targeting the ATP-binding site of the enzyme. Searching the Novartis compound collection for molecules containing this purine motif has allowed the identification of two micromolar hits providing access to a new class of catalytic topoisomerase II inhibitors.
authors: Novartis Institutes for BioMedical Research, WKL-136.P.12, CH-4002 Basel, Switzerland. pascal.furet@novartis.com
authors: Pascal
authors: P
authors: Furet
authors: Joseph
authors: J
authors: Schoepfer
authors: Thomas
authors: T
authors: Radimerski
authors: Patrick
authors: P
authors: Chène
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry*; D020816:Amino Acid Motifs; D001665:Binding Sites; D002384:Catalysis; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019295:Computational Biology / Q000379:methods; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D011687:Purines / Q000737:chemistry; D059005:Topoisomerase II Inhibitors
chemical_list: D004791:Enzyme Inhibitors; D011687:Purines; D059005:Topoisomerase II Inhibitors; D000255:Adenosine Triphosphate