Recent progress with microtubule stabilizers: new compounds, binding modes and cellular activities
TLDR
Recent progress in the chemistry and biology of these diverse microtubule stabilizers focusing on the wide range of organisms that produce these compounds, their mechanisms of inhibiting microtubules-dependent processes, mechanisms of drug resistance, and their interactions with tubulin including their distinct binding sites and modes are covered.About:
This article is published in Natural Product Reports.The article was published on 2014-02-11 and is currently open access. It has received 113 citations till now.read more
Citations
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Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance
Pasarat Khongkow,Ana R. Gomes,Chun Gong,Chun Gong,E P S Man,J W-H Tsang,Fung Zhao,Fung Zhao,Lara J. Monteiro,R. C. Coombes,René H. Medema,Ui-Soon Khoo,E W-F Lam +12 more
TL;DR: It is suggested that paclitaxel targets the FOXM1-KIF20A axis to drive abnormal mitotic spindle formation and mitotic catastrophe and that deregulated FoxM1 and Kif20A expression may confer paclitAXel resistance.
Journal ArticleDOI
Recent advances in microtubule-stabilizing agents
TL;DR: This review focuses on the natural sources, structural features, mechanisms of action, structure-activity relationship (SAR) and chemical synthesis of MSAs, which mainly include paclitaxel, taccalonolides, epothilones, and FR182877 (cyclostreptin).
Journal ArticleDOI
Microtubule-targeting agents and their impact on cancer treatment.
Vladimír Čermák,Vojtěch Dostál,Michael Jelinek,Lenka Libusova,Jan Kovář,Daniel Rösel,Jan Brábek +6 more
TL;DR: In anti-metastatic therapy, MTAs should be combined with other drugs to target all modes of cancer cell invasion, and some of the novel MTAs overcome the resistance mediated by both multidrug resistance transporters as well as overexpression of specific β-tubulin types.
Journal ArticleDOI
Taxanes in cancer treatment: Activity, chemoresistance and its overcoming
TL;DR: Taxanes have been widely used as microtubule-targeting antitumor agents and have shown impact on key molecular mechanisms including disruption of mitotic spindle, mitosis slippage and inhibition of angiogenesis.
Journal ArticleDOI
Synthesis, molecular editing, and biological assessment of the potent cytotoxin leiodermatolide.
Damien Mailhol,Jens Willwacher,Nina Kausch-Busies,Elizabeith E. Rubitski,Zhanna Sobol,Maik Schuler,My-Hanh Lam,Sylvia Musto,Frank Loganzo,Andreas Maderna,Alois Fürstner +10 more
TL;DR: The acquired biodata show that 1 is a potent cytotoxin in human tumor cell proliferation assays, distinguished by GI50 values in the ≤3 nM range even for cell lines expressing the Pgp efflux transporter.
References
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Synthesis and biological evaluation of new paclitaxel analogs and discovery of potent antitumor agents
TL;DR: Taxoids 19a, 19b, 21a, 21b, 23, 27, 29, 34 and 35 were found to exhibit significant anticancer activity against various cancerous cell lines with 23,27, and 29 being the most potent compounds, demonstrating GI50 values of ≤5 nM in several assays.
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Dictyostatin Flexibility Bridges Conformations in Solution and in the β-Tubulin Taxane Binding Site
Ashutosh S. Jogalekar,Krishnan Damodaran,Frederik H. Kriel,Won-Hyuk Jung,Ana A. Alcaraz,Shi Zhong,Dennis P. Curran,James P. Snyder +7 more
TL;DR: Application of several docking methods has identified a low-energy binding model of the DCT/β-tubulin complex (Pose-2/Conf-2) that is gratifyingly compatible with the emerging DCT structure-activity data.
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Cyclostreptin derivatives specifically target cellular tubulin and further map the paclitaxel site.
Enrique Calvo,Isabel Barasoain,Ruth Matesanz,Benet Pera,Emilio Camafeita,Oriol Pineda,Ernest Hamel,Christopher D. Vanderwal,José Manuel Andreu,Juan Antonio López,José Fernando Díaz +10 more
TL;DR: In both types of cells, β-tubulin is identified as the only or the predominantly labeled cellular protein, indicating that covalent binding to microtubules is sufficient to prevent drug efflux mediated by P-glycoprotein.
Journal ArticleDOI
Chemically Diverse Microtubule Stabilizing Agents Initiate Distinct Mitotic Defects and Dysregulated Expression of Key Mitotic Kinases
TL;DR: Delineating how diverse microtubule stabilizers affect mitotic signaling pathways could identify key proteins involved in modulating sensitivity and resistance to the antimitotic actions of these compounds.
Journal ArticleDOI
Synthetic Analogues of the Microtubule-Stabilizing Sponge Alkaloid Ceratamine A Are More Active than the Natural Product
TL;DR: An efficient synthetic route has been developed to 33 that should enable the first in vivo evaluation of the new ceratamine microtubule-stabilizing pharmacophore and has provided several additional analogues for structure-activity relationship evaluation.
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