Identification of small molecules for PI4K2a BRET measurements

National Center For Advancing Translational Sciences

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Abstract

During this period, the collaborative team developed a 384-well cell-based BRET assay to measure PI4K2a activity. Molecular modeling studies were performed to design compounds with increased specificity relative to PI3K. Medicinal chemistry efforts produced novel compounds which were assessed using the cell-based BRET assay to measure PI4P generation on endosomes. In the last year we have greatly progressed toward obtaining more potent and more selective molecules by structure activity relationship studies. The crystal structure of our molecules binging PI4K2a has been resolved, and we are using structural drug-based design to guide the production of new analogues.