Application of Molecular Modeling to Development of New Factor Xa Inhibitors.
In consequence of the key role of factor Xa in the clotting cascade and absence of its activity in the processes that do not affect coagulation, this protein is an attractive target for development of new blood coagulation inhibitors. Factor Xa is more effective and convenient target for creation of...
| Published in: | BioMed Research International Vol. 2015; pp. 1 - 16 |
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| Main Authors: | , , , , , , , , , , |
| Format: | equations & formulas pictorial research tables/charts Journal Article |
| Published: |
Wiley-Blackwell
9/21/2015
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=110155486&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 110155486 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 9/21/2015 vid: 2015 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 110155486 110155486 NLM26484350 110155486 10.1155/2015/120802 NLM26484350 PMC4592935 110155486 ppf: 1 ppct: 15 formats: fmt: @attributes: type: P tig: atl: Application of Molecular Modeling to Development of New Factor Xa Inhibitors. aug: au: Sulimov, Vladimir B. Gribkova, Irina V. Kochugaeva, Maria P. Katkova, Ekaterina V. Sulimov, Alexey V. Kutov, Danil C. Shikhaliev, Khidmet S. Medvedeva, Svetlana M. Krysin, Michael Yu. Sinauridze, Elena I. Ataullakhanov, Fazoil I. affil: Research Computer Center, Moscow State University, Leninskie Gory 1, Building 4, Moscow 119991, Russia sug: subj: Models, Biological Blood Coagulation Factors Enzyme Inhibitors Molecular Structure Proteins In Vitro Studies Binding Sites Descriptive Statistics Data Analysis Software Odds Ratio Confidence Intervals Cell Line Biochemistry Funding Source ab: In consequence of the key role of factor Xa in the clotting cascade and absence of its activity in the processes that do not affect coagulation, this protein is an attractive target for development of new blood coagulation inhibitors. Factor Xa is more effective and convenient target for creation of anticoagulants than thrombin, inhibition of which may cause some side effects. This study is aimed at finding new inhibitors of factor Xa by molecular computer modeling including docking SOL and postdocking optimization DISCORE programs. After validation of molecular modeling methods on well-known factor Xa inhibitors the virtual screening of NCI Diversity and Voronezh State University databases of ready-made low molecular weight species has been carried out. Seventeen compounds selected on the basis of modeling results have been tested experimentally in vitro. It has been found that 12 of them showed activity against factor Xa (IC50 = 1.8-40 μM). Based on analysis of the results, the new original compound was synthesized and experimentally verified. It shows activity against factor Xa with IC50 value of 0.7 μM. pubtype: Academic Journal doctype: equations & formulas pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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