ETP-45658

ETP-45658 is a potent PI3K inhibitor, with IC50s of 22.0 nM, 39.8 nM, 129.0 nM and 717.3 nM for PI3Kα, PI3Kδ, PI3Kβ and PI3Kγ, respectively. ETP-45658 also can inhibit DNA-PK (IC50=70.6 nM) and mTOR (IC50=152.0 nM). ETP-45658 can be used for the research of cancer[1][2].

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

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA-PK

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

Signaling Pathways >> PI3K/Akt/mTOR >> DNA-PK

PI3Kα:22.0 nM (IC50)

PI3Kδ:39.8 nM (IC50)

PI3Kβ:129.0 nM (IC50)

PI3Kγ:717.3 nM (IC50)

mTOR:152.0 nM (IC50)

DNA-PK:70.6 nM (IC50)

ETP-45658 (10 μM; 4 h) decreases in the phosphorylation of FOXO3a, Gsk3-β and p70 S6K in U2OS cells[1]. ETP-45658 inhibits the proliferation of MCF7, PC3, 786-O, HTC116, and U251 cells, with EC50s of 0.48 μM, 0.49 μM, 2.62 μM, 3.53 μM, and 5.56 μM, respectively[1]. ETP-45658 (10 μM; 24 h) induces a clear G1 arrest of PC3 cells[1]. ETP-45658 inhibits the mutant PI3Kα proteins, H1047R and E545K, with IC50s of 16.8 nM and 13.1 nM, respectively[1]. ETP-45658 (5 nM-11.1 μM; 1 h) induces a dose-dependent increase of GFP-FOXO nuclear translocation in U2foxRELOC cells[1]. ETP-45658 (10 μM; 1 h) decrease the expression of cyclin D1 and p-Akt on serine 473 in U2OS cells[1]. Western Blot Analysis[1] Cell Line: U2OS cells Concentration: 10 μM Incubation Time: 4 hours Result: Caused a 95% decrease in the phosphorylation of FOXO3a at threonine 32 and a 55% reduction on Gsk3-β at serine 9. Reduced the phosphorylation of the mTOR substrate p70 S6K.

ETP-45658 (22.7 mg/kg) decreases the level of phosphorylated Akt on serine 473 in the mammary ducts of transgenic mice[1].

[1]. Link W, et, al. Chemical interrogation of FOXO3a nuclear translocation identifies potent and selective inhibitors of phosphoinositide 3-kinases. J Biol Chem. 2009 Oct 9;284(41):28392-28400.

[2]. Hill R, et, al. A novel phosphatidylinositol 3-kinase (PI3K) inhibitor directs a potent FOXO-dependent, p53-independent cell cycle arrest phenotype characterized by the differential induction of a subset of FOXO-regulated genes. Breast Cancer Res. 2014 Dec 9;16(6):482.