Bregman Howard, Williams Douglas S, Atilla G Ekin, Carroll Patrick J, Meggers Eric
Department of Chemistry, University of Pennsylvania, 231 South 34th Street, Philadelphia, Pennsylvania 19104, USA.
J Am Chem Soc. 2004 Oct 27;126(42):13594-5. doi: 10.1021/ja046049c.
Replacing natural products with kinetically inert metal complexes may lead to a new class of therapeutics in which a metal center plays the role of an innocent bystander, organizing the orientation of the organic ligands in the receptor space. As an example of this approach, a ruthenium complex is described that copies the binding mode of indolocarbazole protein kinase inhibitors and serves as a reversible, low-nanomolar inhibitor for glycogen synthase kinase 3 (GSK-3).
用动力学惰性金属配合物取代天然产物可能会催生一类新型治疗药物,其中金属中心扮演着无害旁观者的角色,在受体空间中组织有机配体的取向。作为这种方法的一个例子,描述了一种钌配合物,它模仿吲哚咔唑蛋白激酶抑制剂的结合模式,作为糖原合酶激酶3(GSK-3)的可逆低纳摩尔抑制剂。