원문정보
초록
영어
Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that has recently emerged as a promising target in drug discovery. It is involved in multiple cellular processes and associated with the pathogenesis of several diseases. A three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed on a series of GSK- 3 inhibitors to understand the structural basis for inhibitory activity. Comparative molecular field analysis (CoMFA) method was used to derive 3D-QSAR models. A reliable CoMFA model was developed using ligand-based alignment scheme. The model produced statistically acceptable results with a cross-validated correlation coefficient (q2) of 0.594 and a non-cross-validated correlation coefficient (r2) of 0.943. Robustness of the model was checked by bootstrapping and progressive scrambling analysis. This study could assist in the design of novel compounds with enhanced GSK-3 inhibitory activity.
목차
1. Introduction
2. Methodology
2.1. Data Set
2.2. CoMFA
3. Results and Discussion
3.1. CoMFA Model
3.2. CoMFA Contour Maps
4. Conclusions
Acknowledgements
References
저자정보
참고문헌
- 1A Common Phosphate Binding Site Explains the Unique Substrate Specificity of GSK3 and Its Inactivation by Phosphorylation네이버 원문 이동
- 2Glycogen Synthase Kinase-3 from Rabbit Skeletal Muscle네이버 원문 이동
- 3Potential role of glycogen synthase kinase-3 in skeletal muscle insulin resistance of type 2 diabetes.네이버 원문 이동
- 4Role of GSK‐3β in Alzheimer's disease pathology네이버 원문 이동
- 5Molecular targets of lithium action.네이버 원문 이동
- 6M. K. Rowe, C. Wiest, and D.-M. Chuang, “GSK-3 is a viable potential target for therapeutic intervention in bipolar disorder”, Neurosci. Biobehav. R., Vol. 31, pp. 920-931, 2007.
- 7R. S. Jope and M.-S. Roh, “Glycogen synthase kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions”, Curr. Drug Targets, Vol. 7, pp. 1421-1434, 2006.
- 8Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases네이버 원문 이동
- 9Recent Advances in the Discovery of GSK-3 Inhibitors and a Perspective on their Utility for the Treatment of Alzheimer's Disease네이버 원문 이동
- 10Expression, purification and crystallization of human tau‐protein kinase I/glycogen synthase kinase‐3β네이버 원문 이동