Idelalisib is an orally available first-in-class inhibitor of the PI3K delta enzyme used to treat chronic lymphocytic leukemia, small lymphocytic leukemia, and follicular lymphoma.  Idelalisib’s selectivity for PI3K delta is attributed to the propeller-shaped conformation that it adopts within the enzyme.  By exploiting this conformation, we report a new series of compounds that exhibits greater than 1000x selectivity for delta over the alpha, beta, and gamma isoforms.<br/>

Highly delta selective quinazolinone PI3K inhibitors

255th National Meeting (2018)

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