• Bulletin of the Korean Chemical Society
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• 제27권2호
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• pp.266-272
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• 2006

Three-dimensional quantitative structure-activity relationship (3D-QSAR) models were developed for 67 molecules of 2-amino-benzothiazole-6-anilide derivatives against lymphocyte-specific protein tyrosine kinase (P56 LCK). The molecular field analysis (MFA) and receptor surface analysis (RSA) were employed for QSAR studies and the predictive ability of the model was validated by 15 test set molecules. Structure-based investigations using molecular docking simulation were performed with the crystal structure of P56 LCK. Good correlation between predicted fitness scores versus observed activities was demonstrated. The results suggested that the nature of substitutions at the 2-amino and 6-anilide positions were crucial in enhancing the activity, thereby providing new guidelines for the design of novel P56 LCK inhibitors.

• Bulletin of the Korean Chemical Society
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• 제28권2호
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• pp.200-206
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• 2007

Pharmacophore models for lymphocyte-specific protein tyrosine kinase (P56 LCK) were developed using CATALYST HypoGen with a training set comprising of 25 different P56 LCK inhibitors. The best quantitative pharmacophore hypothesis comprises of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic aliphatic and one ring aromatic features with correlation coefficient of 0.941, root mean square deviation (RMSD) of 0.933 and cost difference (null cost-total cost) of 66.23. The pharmacophore model was validated by two methods and the validated model was further used to search databases for new compounds with good estimated LCK inhibitory activity. These compounds were evaluated for their binding properties at the active site by molecular docking studies using GOLD software. The compounds with good estimated activity and docking scores were evaluated for physiological properties based on Lipinski's rules. Finally 68 compounds satisfied all the properties required to be a successful inhibitor candidate.