Drugs that target dynamic microtubules: a new molecular perspective.
Citations
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Cites background from "Drugs that target dynamic microtubu..."
...…such as cardiotoxicity and neurotoxicity (Ghinet et al., 2013; Hooper et al., 2013; Tozer et al., 2002; Tron et al., 2006), which limit the doses at which chemotherapeutics can be applied, thus impairing their therapeutic value (Dumontet and Jordan, 2010; Gill et al., 2014; Stanton et al., 2011)....
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..., 2006), which limit the doses at which chemotherapeutics can be applied, thus impairing their therapeutic value (Dumontet and Jordan, 2010; Gill et al., 2014; Stanton et al., 2011)....
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268 citations
Cites background from "Drugs that target dynamic microtubu..."
...…studied: the molecular target was recognized, the binding spot was accurately characterized, and the biological consequences of damaging microtubule dynamics were examined; complete reviews summarizing these results are available (Bhattacharyya et al., 2008; Nuki, 2008; Stanton et al., 2011)....
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260 citations
Cites background from "Drugs that target dynamic microtubu..."
...Some of these natural products are presently used in the chemotherapy of cancer [8,12,14]....
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...Sanguinarine is also an inhibitor of microtubule formation [14]....
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196 citations
References
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"Drugs that target dynamic microtubu..." refers background in this paper
...However, it is becoming appreciated that all microtubule-active drugs at low nanomolar concentrations attenuate microtubule dynamicity rather than altering net polymer mass.(4,92,93) Based on this notion, barriers between the two classes seem to be disintegrating and these drugs should be referred to instead as ‘‘suppressors of dynamic instability....
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...No wonder drugs belonging to this class continue to be among the most commonly prescribed agents in cancer chemotherapy.(4,91) Although most microtubule-interfering agents either stabilize or destabilize tubulin via binding on known tubulin-binding sites, there do exist some compounds that bind to tubulin on undefined sites or target microtubules indirectly by altering their posttranslational modification....
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...This blocks dividing cells in mitosis, eventually leading to apoptosis.(4)...
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...Formation of a short polymerization nucleus precedes elongation or polymer growth at each end by the reversible, noncovalent addition of tubulin subunits.(4) For net polymer elongation, the association of tubulin heterodimers into the growing microtubule is faster than microtubule depolymerization....
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3,108 citations
2,484 citations
"Drugs that target dynamic microtubu..." refers background in this paper
...MAPs bind in a nucleotide-insensitive manner to the microtubule lattice.(21) Most MAPs identified to date are posttranslationally regulated by phosphorylation, with the more phosphorylated forms attenuated in their capacity to stabilize microtubules....
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...Assembly of GTP-tubulin and disassembly of GDP-tubulin are both thermodynamically favorable in the cytoplasm and can thus perform mechanical work.(21) The rapid dynamics of spindle microtubules is necessary for the capture of chromosomes during prometaphase, as the spindle fibers have to ‘‘explore’’ the cytoplasmic space to find and make productive attachments to the kinetochores....
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1,632 citations
1,418 citations
"Drugs that target dynamic microtubu..." refers background or methods in this paper
...The orange vector showing the directionality of an RB3/stathmin-like protein and two tubulin complexes are shown superimposed on growing end of microtubule as a reference, as this structure has been used to determine the binding domain of several depolymerizing drugs.(86,87,223) [Color figure canbe viewed in the online issue, which is available at wileyonlinelibrary....
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...Additionally, the stathmin-like protein RB3 has been used to stabilize tubulin in a bent conformation for crystallographic studies to determine the binding sites of several depolymerizing drugs.(86,87)...
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...14), contiguous to the GTP-binding domain of the a-tubulin subunit.(86,118,164,165) It is known to bind to the unpolymerized tubulin subunits in a two-step reaction process that begins with the formation of an initial pre-equilibrium complex, which is reversible and bound with low affinity....
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...Depolymerizing drug, Colchicine is shown as a space-filling model (magenta, highlighted with arrow) at the intradimer interface at the start of the peeling protofilament as determined by Ravelli et al.(86) As in previous figures, the green axis shows direction of growth of a straight protofilament while the cyan axis connects nucleotides of a peeling protofilament....
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