ETP-45658

• CAT Number: I011008
• CAS Number: 1198357-79-7
• Molecular Formula: C16H17N5O2
• Molecular Weight: 311.34
• Purity: ≥95%
• Synonyms: 3-(1-methyl-4-morpholin-4-ylpyrazolo[3,4-d]pyrimidin-6-yl)phenol
• InChI: InChI=1S/C16H17N5O2/c1-20-15-13(10-17-20)16(21-5-7-23-8-6-21)19-14(18-15)11-3-2-4-12(22)9-11/h2-4,9-10,22H,5-8H2,1H3
• InChIKey: BJVRNXSHJLDZJR-UHFFFAOYSA-N
• SMILES: CN1C2=C(C=N1)C(=NC(=N2)C3=CC(=CC=C3)O)N4CCOCC4

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

Reference

[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.
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[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 De
 [Content Brief]