PI3K-IN-4 is a potent pan-PI3K inhibitor demonstrating high activity across three PI3K isoforms with picomolar IC50 values. It exhibits excellent inhibitory activity against PI3Kα (IC50 = 0.20 nM), PI3Kβ (IC50 = 2.99 nM), PI3Kδ (IC50 = 0.48 nM), and PI3Kγ (IC50 = 0.58 nM), but shows no significant activity against EGFR. By interfering with the PI3K/Akt signaling pathway, PI3K-IN-4 hinders cancer cell proliferation, blocks colony formation, and induces apoptosis (apoptosis). This compound is applicable in research related to lung cancer, colon cancer, and breast cancer.

PI3Kα:0.20 nM

PI3K-IN-4 (compound 7b) exhibits antiproliferative activity against common human cancer cells, with IC 50 values of 3.10 μM for A549, 0.33 μM for HCT116, and 0.22 μM for MCF-7, while demonstrating lower cytotoxicity in HUVEC (IC 50 = 19.6 μM) and HL7702 normal cells (IC 50 = 60.0 μM). At concentrations of 0.1-10 μM, PI3K-IN-4 reduces phosphorylation of Akt protein at the S473 site in a dose-dependent manner and decreases the p-Akt/Akt ratio, suggesting it inhibits MCF-7 cell growth via the PI3K/Akt signaling pathway. It also dose-dependently inhibits colony formation and proliferation of MCF-7 cells at 0.2-0.8 μM over 72 hours. Moreover, PI3K-IN-4 induces apoptosis in MCF-7 cells, evident by pronounced nuclear fragmentation and chromatin condensation, at concentrations of 0.2-0.8 μM over 48 hours. The formation of four critical hydrogen bonds with PI3K, one more than Omipalisib, may contribute to PI3K-IN-4’s enhanced binding stability and activity.