From Fragment-screening to Fragment-growing - new strategies for drug discovery

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Type-2 diabetes represents a major and growing health problem in particular in industrialised countries. Although many cases may be preventable by life-style changes and better diet, numbers are steadily rising. Human Glucose Kinase (GK) has been identified as one potential target for intervention but so far, no drug targeting this protein has entered the market. In this project we will employ and develop fragment-based methods to identify new lead compounds binding to GK. Over the last decade, fragment-based methods have made a major impact on drug discovery in academia and pharmaceutical research. Recent advances in high-throughput structure determination and the development of targeted fragment libraries were instrumental, however, one of the remaining bottlenecks is the translation from multiple fragment binding sites into a credible lead compound. The overall goal of the proposed project is to identify new chemical entities that act as allosteric activators of human GK and present lead candidates for future drug development using a new fragment-based drug discovery approach. These efforts will be supported with the expertise from CCDC to develop new algorithms to support fragment-linking and growing approach.