PIP4K-IN-a131 is a selective inhibitor of PIP4K lipid kinases, demonstrating IC50 values of 1.9 μM for PIP4K2A and 0.6 μM for PIP4Ks. It exhibits cancer-selective lethality by simultaneously blocking the lipid kinase PIP4Ks and mitotic pathways.

PIP4Ks:0.6 µM (IC50), PIP4K2A:1.9 µM (IC50)

PIP4K-IN-a131 (0-100 μM; 72 hours) is a potent antiproliferative agent with selectivity for killing cancer cells via a dual-inhibitory mechanism. It inhibits the PI3K/Akt/mTOR pathway in normal BJ cells but not in transformed counterparts, causing G1/S phase arrest by transcriptionally upregulating PIK3IP1. In a Cell Proliferation Assay using normal and transformed BJ cells, PIP4K-IN-a131 (0-100 μM) selectively killed cancer cells after 72 hours. In RT-PCR, BJ cells treated with PIP4K-IN-a131 (5 μM; 24 hours) showed upregulation of PIK3IP1 mRNA levels.