Abstract
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.
Graphical Abstract
Current Topics in Medicinal Chemistry
Title:Target Driven Preclinical Screening for New Antimitotic Chemotherapy Agents
Volume: 14 Issue: 20
Author(s): S. Novio, M. Freire-Garabal and M.J. Núnez
Affiliation:
Keywords: Cancer, drug development, kinase, kinesin, mitosis, multiprotein complexes.
Abstract: 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.
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Novio S., Freire-Garabal M. and Núnez M.J., Target Driven Preclinical Screening for New Antimitotic Chemotherapy Agents, Current Topics in Medicinal Chemistry 2014; 14 (20) . https://dx.doi.org/10.2174/1568026614666141130093425
DOI https://dx.doi.org/10.2174/1568026614666141130093425 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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