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- Title
A Computational Study on Thiourea Analogs as Potent MK-2 Inhibitors.
- Authors
Ming Hao; Hong Ren; Fang Luo; Shuwei Zhang; Jieshan Qiu; Mingjuan Ji; Hongzong Si Guohui Li
- Abstract
Mitogen-activated protein kinase-activated protein kinase 2 (MK-2) has been identified as a drug target for the treatment of inflammatory diseases. Currently, a series of thiourea analogs as potent MK-2 inhibitors were studied using comprehensive computational methods by 3D-QSAR, molecular docking and molecular dynamics simulations for a further improvement in activities. The optimal 3D models exhibit high statistical significance of the results, especially for the CoMFA results with r² ncv, q² values of 0.974, 0.536 for the internal validation, and r² pred, r² m values of 0.910, 0.723 for the external validation and Roy's index, respectively. In addition, more rigorous validation criteria suggested by Tropsha were also employed to check the built models. Graphic representation of the results, as contoured 3D coefficient plots, also provides a clue to the reasonable modification of molecules: (i) The substituent with a bulky size and electron-rich group at the C5 position of the pyrazine ring
- Subjects
THIOUREA; MITOGEN-activated protein kinases; ENZYME inhibitors; INFLAMMATION treatment; QSAR models; MOLECULAR docking
- Publication
International Journal of Molecular Sciences, 2012, Vol 13, Issue 6, p7057
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms13067057