pi3kα-in-14

PI3Kα-IN-14 (compound F8), a potent PI3Kα inhibitor, exhibits an IC50 value of 0.14 nM and significantly reduces mitochondrial membrane potential, leading to G1 phase cell cycle arrest and apoptosis in U87-MG cells. It also shows substantial antiproliferative effects against various tumor cell lines, including PC-3 (IC50 of 0.28 μM), HCT-116 (IC50 of 0.57 μM), and U87-MG (IC50 of 1.37 μM) [1].

PI3Kδ-IN-14 (Compound (S)-29), a selective PI3Kδ inhibitor with an IC50 of 0.8 nM and a Kd of 84.8 nM, targets the ATP-binding site within the kinase domain of PI3Kδ, exhibiting anti-inflammatory properties by impeding the PI3K AKT pathway and alleviating acute lung injury (ALI) [1].

Apitolisib (RG 7422), an effective, class I PI3K inhibitor for PI3Kα(IC50=5 nM), PI3Kβ(IC50=27 nM), PI3Kδ(IC50=7 nM), PI3Kγ (IC50=14 nM), is used in trials study of solid cancers, breast cancer, prostate cancer, renal cell carcinoma, and endometrial carcinoma, among others.

CH5132799 has been used in trials studying the treatment of Solid Tumors.

PKI-179 is an orally bioavailable dual inhibitor of PI3K and mammalian target of rapamycin (mTOR). In an in vitro enzymatic assay, it potently inhibits PI3K (IC50s = 8, 24, 17, and 74 nM for isoforms α, β, δ, and γ, respectively), two common PI3Kα mutants, E545K and H1047R (IC50s = 14 and 11 nM, respectively), and mTOR (IC50 = 0.42 nM). PKI-179 is selective for PI3K and mTOR over a panel of 361 other kinases at IC50 values up to 50 μM, hERG (IC50 > 30 μM), and cytochrome P450 (CYP) isoforms (IC50s > 30 μM), but does have activity for CYP2C8 (IC50 = 3 μM). It inhibits proliferation through the Akt/mTOR signaling pathway in MDA-361 breast and PC3MM2 prostate cancer cell lines in vitro (IC50s = 22 and 29 nM, respectively) and inhibits tumor growth in an MDA-361 mouse xenograft model when used at a dose of 50 mg/kg.