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Application of Molecular Modeling to Urokinase Inhibitors Development
Joint Authors
Sulimov, A. V.
Oferkin, I. V.
Sadovnichiy, V. A.
Roschin, A. I.
Katkova, E. V.
Romanov, A. N.
Sulimov, V. B.
Tkachuk, V. A.
Plekhanova, O. S.
Beloglazova, I. B.
Source
Issue
Vol. 2014, Issue 2014 (31 Dec. 2014), pp.1-15, 15 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2014-05-20
Country of Publication
Egypt
No. of Pages
15
Main Subjects
Abstract EN
Urokinase-type plasminogen activator (uPA) plays an important role in the regulation of diverse physiologic and pathologic processes.
Experimental research has shown that elevated uPA expression is associated with cancer progression, metastasis, and shortened survival in patients, whereas suppression of proteolytic activity of uPA leads to evident decrease of metastasis.
Therefore, uPA has been considered as a promising molecular target for development of anticancer drugs.
The present study sets out to develop the new selective uPA inhibitors using computer-aided structural based drug design methods.
Investigation involves the following stages: computer modeling of the protein active site, development and validation of computer molecular modeling methods: docking (SOL program), postprocessing (DISCORE program), direct generalized docking (FLM program), and the application of the quantum chemical calculations (MOPAC package), search of uPA inhibitors among molecules from databases of ready-made compounds to find new uPA inhibitors, and design of new chemical structures and their optimization and experimental examination.
On the basis of known uPA inhibitors and modeling results, 18 new compounds have been designed, calculated using programs mentioned above, synthesized, and tested in vitro.
Eight of them display inhibitory activity and two of them display activity about 10 μM.
American Psychological Association (APA)
Sulimov, V. B.& Katkova, E. V.& Oferkin, I. V.& Sulimov, A. V.& Romanov, A. N.& Roschin, A. I.…[et al.]. 2014. Application of Molecular Modeling to Urokinase Inhibitors Development. BioMed Research International،Vol. 2014, no. 2014, pp.1-15.
https://search.emarefa.net/detail/BIM-486110
Modern Language Association (MLA)
Sulimov, V. B.…[et al.]. Application of Molecular Modeling to Urokinase Inhibitors Development. BioMed Research International No. 2014 (2014), pp.1-15.
https://search.emarefa.net/detail/BIM-486110
American Medical Association (AMA)
Sulimov, V. B.& Katkova, E. V.& Oferkin, I. V.& Sulimov, A. V.& Romanov, A. N.& Roschin, A. I.…[et al.]. Application of Molecular Modeling to Urokinase Inhibitors Development. BioMed Research International. 2014. Vol. 2014, no. 2014, pp.1-15.
https://search.emarefa.net/detail/BIM-486110
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-486110