Inhibitors of kinesin motor proteins--research and clinical progress.
Molecules targeting mitosis, and specifically compounds targeting microtubule stability, are important in the treatment of cancer. Unfortunately, the mechanism of action of these agents can cause undesirable toxicities to healthy cells, inducing neurotoxicity and neutropenia in patients. In addition, many of these agents are subject to acquired resistance, usually through increased expression of membrane P-glycoprotein pumps. Due to the clinically proven utility of antimitotic therapeutics, the discovery of new agents with different mechanisms of action which may allow for the development of less toxic oncolytic treatments is highly desirable. This review describes key advances made over the last year toward the design and development of inhibitors of kinesin motor proteins, with particular emphasis placed on non-ATP-competitive, small-molecule inhibitors of kinesin spindle protein (Eg5).
Duhl
David M
DM
Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA.
Renhowe
Paul A
PA
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors; D002455:Cell Division / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors*; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C470243:KIF11 protein, human; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016547:Kinesins