RESUMEN
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).
Asunto(s)
Antineoplásicos/farmacología , Cinesinas/antagonistas & inhibidores , Animales , Antifúngicos/farmacología , Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Proteínas de Ciclo Celular/antagonistas & inhibidores , División Celular/efectos de los fármacos , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Humanos , Proteínas Supresoras de Tumor/antagonistas & inhibidoresRESUMEN
The identification of a highly efficacious anti-obesity agent remains an illusive goal. While many avenues of investigation have been pursued, none of the existing compounds claim much more than a 10% reduction in weight in humans (over a one year period with diet and exercise). Nonetheless, the potential reward for fulfilling this unmet medical need has kept interest levels high in the research community. The recent explosion of genetic information has identified numerous potential targets for drug screening. The melanocortin-4 receptor is a promising target and is currently being intensively investigated by many companies and academic research groups.