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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Metabolites of Vinca Alkaloid Vinblastine: Tubulin Binding and Activation of Nausea-Associated Receptors.
TL;DR: The hydroxyl group added upon metabolism of VLB suggests that it can also be a reasonable starting compound for designing the next generation of antimitotic drugs to overcome P-glycoprotein-mediated multidrug resistance, which is often observed with vinca alkaloids.
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Markus Grosch,Sebastian Ittermann,Ejona Rusha,Tobias Greisle,Chaido Ori,Dong-Jiunn Jeffery Truong,Adam C. O’Neill,Anna Pertek,Gil G. Westmeyer,Micha Drukker +9 more
TL;DR: Positive correlation between the size of the nucleus and the number of paraspeckles exist in numerous types of human cells, and the structure-function relationship of lncRNAs that regulates stem cell differentiation is likely to be determined by the dynamics of nucleus size and binding site accessibility.
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The microtubule-associated histone methyltransferase SET8, facilitated by transcription factor LSF, methylates α-tubulin.
Hang Gyeong Chin,Hang Gyeong Chin,Pierre-Olivier Estève,Cristian I. Ruse,Jiyoung Lee,Scott E. Schaus,Sriharsa Pradhan,Ulla Hansen +7 more
TL;DR: These findings suggest the general model that microtubule-associated proteins, including transcription factors, recruit or stimulate protein-modifying enzymes to target tubulins and point to dual functions for SET8 and LSF not only in chromatin regulation but also in cytoskeletal modification.
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The Frequent Sampling of Wound Scratch Assay Reveals the "Opportunity" Window for Quantitative Evaluation of Cell Motility-Impeding Drugs.
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Phase II study of the antibody-drug conjugate TAK-264 (MLN0264) in patients with metastatic or recurrent adenocarcinoma of the stomach or gastroesophageal junction expressing guanylyl cyclase C
Khaldoun Almhanna,Maria Luisa Limon Miron,David Wright,Antonio Cubillo Gracian,Richard A. Hubner,Jean-Luc Van Laethem,Carolina Muriel Lopez,Maria Alsina,Frederico Longo Muñoz,Johanna C. Bendell,Irfan Firdaus,Wells A. Messersmith,Zhan Ye,Adedigbo Fasanmade,Hadi Danaee,Thea Kalebic +15 more
TL;DR: TAK-264 demonstrated a manageable safety profile in this patient population of patients with adenocarcinoma of the stomach or gastroesophageal junction expressing GCC and did not support continuation to stage II of the study.
References
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