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Computer Design of Low-Molecular-Weight Inhibitors of Coagulation Factors

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Abstract

The review discusses main approaches to searching for new low-molecular-weight inhibitors of coagulation factors IIa, Xa, IXa, and XIa and the results of such studies conducted from 2015 to 2018. For each of these factors, several inhibitors with IC50 < 10 nM have been found, some of which are now tested in clinical trials. However, none of the identified inhibitors meets the requirements for an “ideal” anticoagulant, so further studies are required.

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Abbreviations

ADME:

absorption, distribution, metabolism, excretion

ADMET (ADME/Tox):

absorption, distribution, metabolism, excretion, toxicity

ATIII:

antithrombin III

CoMFA:

comparative molecular field analysis

CoMSIA:

com-parative molecular similarity indices analysis

DOACs:

direct oral anticoagulants

DTIs:

direct thrombin inhibitors

LBDD:

ligand-based drug design

PASS:

prediction of activity spectra for substances

QSAR:

quantitative structure-activity relation-ships

SBDD:

structure-based drug design

TF:

tissue factor

TFPI:

tissue factor pathway inhibitor

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Authors and Affiliations

  1. Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, 119991, Moscow, Russia

    A. S. Kabankin, E. I. Sinauridze, E. N. Lipets & F. I. Ataullakhanov

  2. Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 117997, Moscow, Russia

    E. I. Sinauridze, E. N. Lipets & F. I. Ataullakhanov

  3. Lomonosov Moscow State University, Faculty of Physics, 119991, Moscow, Russia

    F. I. Ataullakhanov

  4. Moscow Institute of Physics and Technology, 141701, Dolgoprudny, Moscow Region, Russia

    F. I. Ataullakhanov

Authors
  1. A. S. Kabankin
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  2. E. I. Sinauridze
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  3. E. N. Lipets
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  4. F. I. Ataullakhanov
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Corresponding author

Correspondence to F. I. Ataullakhanov.

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Russian Text © A. S. Kabankin, E. I. Sinauridze, E. N. Lipets, F. I. Ataullakhanov, 2019, published in Biokhimiya, 2019, Vol. 84, No. 2, pp. 191–211.

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Kabankin, A.S., Sinauridze, E.I., Lipets, E.N. et al. Computer Design of Low-Molecular-Weight Inhibitors of Coagulation Factors. Biochemistry Moscow 84, 119–136 (2019). https://doi.org/10.1134/S0006297919020032

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  • DOI: https://doi.org/10.1134/S0006297919020032

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