Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 18, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/ijms18122508
Keywords
microtubules; kinase inhibitor; dual inhibitor; mitotic arrest; intracellular traffic
Funding
- JSPS KAKENHI [JP17K07347]
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [17K07347] Funding Source: KAKEN
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Microtubule-targeting agents are widely used as clinical drugs in the treatment of cancer. However, some kinase inhibitors can also disrupt microtubule organization by directly binding to tubulin. These unexpected effects may result in a plethora of harmful events and/or a misinterpretation of the experimental results. Thus, further studies are needed to understand these dual inhibitors. In this review, I discuss the roles of dual inhibitors of kinase activity and microtubule function as well as describe the properties underlining their dual roles. Since both kinase and microtubule inhibitors cause cell toxicity and cell cycle arrest, it is difficult to determine which inhibitor is responsible for each phenotype. A discrimination of cell cycle arrest at G0/G1 or G2/M and/or image analyses of cellular phenotype may eventually lead to new insights on drug duality. Because of the indispensable roles of microtubules in mitosis and vesicle transport, I propose a simple and easy method to identify microtubule depolymerizing compounds.
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