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Computer Modeling and Synthesis of Potential Inhibitors of Tyrosine Kinase BCR-ABL with the T315I Mutation

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Abstract—

A comparative analysis of the interaction of the chimeric protein BCR-ABL, of the normal type and with the T315I mutation, with known inhibitors as well as compounds potentially capable of inhibiting the mutant protein has been carried out by computer modeling. It has been shown that the compounds proposed are incorported into the structure of the protein with the retention of the basic hydrogen bonds and intermolecular interactions. Two structures containing the pyrrole cycle have been synthesized, which, according to the results of computer modeling, appear to be most promising.

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Authors and Affiliations

  1. Institute of Physical and Organic Chemistry, National Academy of Sciences of Belarus, 220072, Minsk, Belarus

    A. N. Fedarkevich, O. L. Sharko & V. V. Shmanai

Authors
  1. A. N. Fedarkevich
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  2. O. L. Sharko
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  3. V. V. Shmanai
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Correspondence to A. N. Fedarkevich.

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The paper does not contain any studies involving animals or human participants performed by any of the authors.

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The authors declare that there is no conflict of interest.

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Translated by S. Sidorova

Abbreviations: DMF-DMA, dimethylformamide diethyl acetal; DMAP, dimethylaminopyridine; DCC, dicyclohexylcarbodiimide; PE, petroleum ether.

Corresponding author: phone: +3 (754) 479-257-04; e-mail: artem.fedorkevich@gmail.com.

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Fedarkevich, A.N., Sharko, O.L. & Shmanai, V.V. Computer Modeling and Synthesis of Potential Inhibitors of Tyrosine Kinase BCR-ABL with the T315I Mutation. Russ J Bioorg Chem 46, 187–198 (2020). https://doi.org/10.1134/S1068162020020089

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  • DOI: https://doi.org/10.1134/S1068162020020089

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