Drugs that target dynamic microtubules: a new molecular perspective.
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TLDR
The effects of microtubule‐binding chemotherapeutic agents are reviewed from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of micro Tubule assembly or disassembly.Abstract:
Microtubules have long been considered an ideal target for anticancer drugs because of the essential role they play in mitosis, forming the dynamic spindle apparatus. As such, there is a wide variety of compounds currently in clinical use and in development that act as antimitotic agents by altering microtubule dynamics. Although these diverse molecules are known to affect microtubule dynamics upon binding to one of the three established drug domains (taxane, vinca alkaloid, or colchicine site), the exact mechanism by which each drug works is still an area of intense speculation and research. In this study, we review the effects of microtubule-binding chemotherapeutic agents from a new perspective, considering how their mode of binding induces conformational changes and alters biological function relative to the molecular vectors of microtubule assembly or disassembly. These “biological vectors” can thus be used as a spatiotemporal context to describe molecular mechanisms by which microtubule-targeting drugs work.read more
Citations
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Deciphering the Binding Mechanism of Noscapine with Lysozyme: Biophysical and Chemoinformatic Approaches.
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Synthesis and biological evaluation of novel chalcone derivatives as a new class of microtubule destabilizing agents.
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Microtubules as a Critical Target for Arsenic Toxicity in Lung Cells in Vitro and in Vivo
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Determination of Noscapine’s Localization and Interaction with the Tubulin-α/β Heterodimer
TL;DR: Noscapine is found to function as a tubulin‐stabilizing agent that interacts strongest with the lateral and longitudinal segments of the tubulin dimer, impacting the interaction between monomers in neighboring protofilaments.
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3-Amino-thieno[2,3-b]pyridines as microtubule-destabilising agents: Molecular modelling and biological evaluation in the sea urchin embryo and human cancer cells.
Chatchakorn Eurtivong,Victor V. Semenov,Marina N. Semenova,Leonid D. Konyushkin,Olga P. Atamanenko,Jóhannes Reynisson,Alex S. Kiselyov +6 more
TL;DR: It is demonstrated that for the 3-amino-thieno[2,3-b]pyridines the most effective mechanism of action is microtubule-destabilisation initiated by binding to the colchicine pocket.
References
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Mary Ann Jordan,Leslie Wilson +1 more
TL;DR: Highly dynamic mitotic-spindle microtubules are among the most successful targets for anticancer therapy, and it is now known that at lower concentrations, microtubule-targeted drugs can suppress micro Tubule dynamics without changingmicrotubule mass; this action leads to mitotic block and apoptosis.
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Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain
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