Binding modes of cabazitaxel with the different human beta-tubulin isotypes: DFT and MD studies.

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Zhu L, Zhang C, Lu X, Song C, Wang C, Zhang M, Xie Y, Schaefer HF 3rd

Binding modes of cabazitaxel with the different human beta-tubulin isotypes: DFT and MD studies.

J Mol Model. 2020 May 30;26(6):162. doi: 10.1007/s00894-020-04400-w.

PubMed ID

32474655 [ View in PubMed

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Abstract

Taxanes (paclitaxel, docetaxel, cabazitaxel) are anticancer drugs as microtubule inhibitors. Following our previous studies on paclitaxel and docetaxel, in this work, we examine cabazitaxel and compare these three taxenes. The binding interaction of three taxanes with various beta-tubulin isotypes is studied by homology modeling, molecular docking, and molecular dynamics simulations. The results show that the effects of docetaxel on betaI-tubulin (- 29.5 kcal/mol) and of paclitaxel on betaIIa-tubulin (- 25.5 kcal/mol) are much stronger than their effects on betaIII-tubulin (- 17.8 kcal/mol and - 8.6 kcal/mol, respectively). However, the effect of cabazitaxel on betaIII-tubulin (- 23.0 kcal/mol) is comparable with that on betaI-tubulin (- 24.0 kcal/mol) and betaIIa-tubulin (- 25.9 kcal/mol), consistent with the fact that overexpression of betaIII-tubulin increases the drug resistance to paclitaxel and docetaxel, but has little influence for cabazitaxel. This theoretical research supports the use of cabazitaxel for patients who are resistant to the action of paclitaxel and docetaxel.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cabazitaxel	Tubulin beta-1 chain	Protein	Humans	Yes	Inhibitor	Details