Discovery of a new class of catalytic topoisomerase II inhibitors targeting the ATP-binding site by structure based design. Part I

作者：Furet Pascal^*; Schoepfer Joseph; Radimerski Thomas; Chene Patrick

来源：Bioorganic & Medicinal Chemistry Letters, 2009, 19(15): 4014-4017.

DOI：10.1016/j.bmcl.2009.06.034

• Anticancer agents
• Structure based design
• ATPase inhibitors
• Topoisomerase II inhibitors

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.

• 出版日期2009-8-1