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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Target Driven Preclinical Screening for New Antimitotic Chemotherapy Agents

Author(s): S. Novio, M. Freire-Garabal and M.J. Núnez

Volume 14, Issue 20, 2014

Page: [2263 - 2271] Pages: 9

DOI: 10.2174/1568026614666141130093425

Price: $65


Currently approved antimitotic therapies used in chemotherapy are microtubule-targeting agents (MTAs). Despite they achieved some level of success, they have limited efficacy as single agents, with issues of slippages and resistance, and cause significant side effects. The advances in the identification of other mitosis-related targets led to the development of new mitotic regulators aimed to perturb mitosis without interfering with microtubule dynamics in non-dividing cells trying to reduce side effects in patients. Some of these compounds like those targeted to entry and mitotic kinases, mitotic kinesins/motor proteins, and multiprotein complexes have been evaluated in vitro and in animal models, and some of them have reached clinical trials. Despite promising preclinical results, in many cases, the efficacy demonstrated by these new antimitotics was not better than current microtubule inhibitors. In this paper we review present and future strategies on the search for new antimitotic compounds based on identification of new protein targets and development of multifunctional inhibitors of mitosis in cancer cells.

Keywords: Cancer, drug development, kinase, kinesin, mitosis, multiprotein complexes.

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