PI3K/mTOR Inhibitor-1

PI3K/mTOR Inhibitor-1 is a potent, orally bioavailable dual PI3K/mTOR inhibitor with IC50s of 20/376/204/46 nM and 186 nM for PI3Kα/PI3Kβ/PI3Kγ/PI3Kδ and mTOR, respectively[1]. Antitumor activity[1].

Research Areas >> Cancer

Signaling Pathways >> PI3K/Akt/mTOR >> PI3K

PI3Kα:20 nM (IC50)

PI3Kβ:376 nM (IC50)

PI3Kγ:204 nM (IC50)

PI3Kδ:46 nM (IC50)

mTOR:186 nM (IC50)

PI3K/mTOR Inhibitor-1 (Compound 26) also exhibits potent functional suppression of AKT phosphorylation (IC50=196 nM), and excellent antiproliferative effects on a panel of cancer cells[1]. PI3K/mTOR Inhibitor-1 exhibits excellent antiproliferative effects on a panel of cancer cells. PI3K/mTOR Inhibitor inhibits A431, A549, PC3, MDA-MB-361, SW480, ES-2, HT29, SK-OV-3, HCT116 , G401 , BT20 ,DLD1 HCC827, H1650, H460, Farage, H820, HCT15, H358, Colo-205, PC9, H1975, WSU-DLCL2, HT, A2780, SU-DHL-10, Toledo,SU-DHL-6, DB, and Pfeiffer cells with IC50s of 0.188, 0.104, 0.063, 0.085, 0.534, 0.179, 0.163, 0.135, 0.308, 0.113, 0.729, 0.264, 0.287, 1.662, 0.611, 0.202, 0.365, 0.104, 0.098, 0.109, 0.237, 0.136, 0.145, 0.090, 0.251 0.215, 0.269, 0.111 0.062, and 0.061 µM, respectively[1].

PI3K/mTOR Inhibitor-1 (Compound 26) produces 54.4% tumor growth inhibition (TGI) with daily oral doses of 3.75 mg/kg for 27 days. The 7.5 mg/kg group of PI3K/mTOR Inhibitor-1 displays more significant TGI (72.9%). All animals survive after 27-day treatment, whereas 15% weigh loss is observed in PI3K/mTOR Inhibitor-1, 7.5 mg/kg group[1].

[1]. Shen S, et al. Discovery of an Orally Bioavailable Dual PI3K/mTOR Inhibitor Based on Sulfonyl-Substituted Morpholinopyrimidines. ACS Med Chem Lett. 2018 Jun 25;9(7):719-724.