molecules of the month

The first non-ATP-competitive inhibitor of the long-pursued PI3Kδ kinase. Phosphatidylinositol-3-kinase (PI3K) has received intense attention as a drug target from the pharmaceutical industry due to its central role in cancer and involvement in other indications. As described in our recent overview of this area, numerous compounds have entered clinical trials for this target, and six PI3K inhibitors have been approved (five in cancers). However, a number of these drugs have exhibited significant toxicity issues, resulting in black box warnings and subsequent partial or full withdrawals due to safety concerns. Roginolisib (IOA-244) is the first non-ATP-competitive PI3Kδ inhibitor whose novel chemotype may help assess whether different human safety profiles may be achievable with PI3Kδ inhibition. PI3Kδ isoform-selectivity achieved with ATP-competitive inhibitors…