PI-103

• CAT Number: I003366
• CAS Number: 371935-74-9
• Molecular Formula: C₁₉H₁₆N₄O₃
• Molecular Weight: 348.36
• Purity: ≥95%
• Synonyms: 3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol
• Target: Cell Cycle/DNA Damage
• Solubility: DMSO ≥22mg/mL Water <1.2mg/mL Ethanol <1.2mg/mL
• Storage: 3 years -20℃ powder
• IC50: 2 nM/3 nM/3 nM/15 nM (p110α/β/δ/γ)
• IUPAC Name: 3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenol
• InChI: InChI=1S/C19H16N4O3/c24-13-4-1-3-12(11-13)17-21-15-14-5-2-6-20-19(14)26-16(15)18(22-17)23-7-9-25-10-8-23/h1-6,11,24H,7-10H2
• InChIKey: TUVCWJQQGGETHL-UHFFFAOYSA-N
• SMILES: C1COCCN1C2=NC(=NC3=C2OC4=C3C=CC=N4)C5=CC(=CC=C5)O

PI-103（Cat No.:I003366）is a potent dual inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR), two critical enzymes in the PI3K/Akt/mTOR signaling pathway. By targeting both PI3K and mTOR, PI-103 disrupts processes such as cell proliferation, survival, and metabolism, making it valuable for cancer research. It is particularly effective in studying tumors with dysregulated PI3K signaling, including glioblastoma and other aggressive cancers. PI-103 is commonly used in preclinical studies to explore its therapeutic potential and to investigate resistance mechanisms to targeted cancer therapies.

Reference

[1]. Westhoff, M.-A.; Kandenwein, J. A.; Karl, S.; Vellanki, S. H. K.; Braun, V.; The pyridinylfuranopyrimidine inhibitor, PI-103, chemosensitizes glioblastoma cells for apoptosis by inhibiting DNA repair. Oncogene (2009), 28(40), 3586-3596.
Abstract
The failure of conventional therapies in glioblastoma (GBM) is largely due to an aberrant activity of survival cascades, such as PI3 kinase (PI3K)/Akt-mediated signaling. This study is the first to show that the class I PI3K inhibitor, PI-103, enhances chemotherapy-induced cell death of GBM cells. Concurrent treatment with PI-103 and DNA-damaging drugs, in particular doxorubicin, significantly increases apoptosis and reduces colony formation compared with chemotherapy treatment alone. The underlying molecular mechanism for this chemosensitization was shown by two independent approaches, that is, pharmacological and genetic inhibition of PI3K, DNA-PK and mTOR, to involve inhibition of DNA-PK-…
[2]. Park, S.; Chapuis, N.; Bardet, V.; Tamburini, J.; Gallay, N.; Willems, L.; PI-103, a dual inhibitor of Class IA phosphatidylinositide 3-kinase and mTOR, has antileukemic activity in AML. Leukemia (2008), 22(9), 1698-1706.
Abstract
The phosphatidylinositol 3-kinase (PI3K)/Akt and mammalian target of rapamycin complex 1 (mTORC1) signaling pathways are frequently activated in acute myelogenous leukemia (AML). mTORC1 inhibition with RAD001 induces PI3K/Akt activation and both pathways are activated independently, providing a rationale for dual inhibition of both pathways. PI-103 is a new potent PI3K/Akt and mTOR inhibitor. In human leukemic cell lines and in primary blast cells from AML patients, PI-103 inhibited constitutive and growth factor-induced PI3K/Akt and mTORC1 activation. PI-103 was essentially cytostatic for cell lines and induced cell cycle arrest in the G1 phase. In blast cells, PI-103 inhibited leukemic pro…
[3]. Segerstrom L, et al. Effects of small molecule inhibitors of PI3K/Akt/mTOR signaling on neuroblastoma growth in vitro and in vivo. Int J Cancer. 2011 Dec 15;129(12):2958-65.

[4]. Bagci-Onder T, et al. A dual PI3K/mTOR inhibitor, PI-103, cooperates with stem cell-delivered TRAIL in experimental glioma models. Cancer Res. 2011 Jan 1;71(1):154-63.