| Identification | Back Directory | [Name]
PI-103 | [CAS]
371935-74-9 | [Synonyms]
PI 103 HYDROCHLORIDE
PI-103HydrochlorideSalt
PI-103, Free Base, >99%
PI 3-Kinase Inhibitor (PI-103) B-0303
3-(4-Morpholinopyrido[3',2':4,5]
furo[3,2-d]pyriMidin-2-yl)phenol
3-[4-Morpholin-4-ylpyrido[3',2':4,5]furo[3,2-d]pyriMidin-2-yl]phenol
3-[4-(4-Morpholinylpyrido[3',2',4,5]furo[3,2-d]pyrimidin-2-yl]phenol
Phenol, 3-[4-(4-Morpholinyl)pyrido[3',2':4,5]furo[3,2-d]pyriMidin-2-yl]-
PI 103
3-[4-(4-Morpholinylpyrido[3',2',4,5]furo[3,2-d]pyrimidin-2-yl]phenol
3-(4-morpholinopyrido[3',2':4,5]furo[3,2-d]pyrimidin-2-yl)phenol hydrochloride
3-[4-(4-MORPHOLINYLPYRIDO)[3',2':4,5]FURO[3,2-D]PYRIMIDIN-2-YL]PHENOL HYDROCHLORIDE
3-[4-(4-Morpholinylpyrido[3',2',4,5]furo[3,2-d]pyrimidin-2-yl]phenol PI 103 | [Molecular Formula]
C19H16N4O3.ClH | [MDL Number]
MFCD10687102 | [MOL File]
371935-74-9.mol | [Molecular Weight]
384.821 |
| Chemical Properties | Back Directory | [density ]
1.409±0.06 g/cm3(Predicted) | [storage temp. ]
Desiccate at +4°C | [solubility ]
Soluble in DMSO (up to 40 mg/ml) | [form ]
White solid | [pka]
9.06±0.10(Predicted) | [color ]
White | [Stability:]
Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 2 months. |
| Hazard Information | Back Directory | [Biological Activity]
Inhibitor of DNA-PK, PI 3-kinase (p110 α ) and mTOR (IC 50 values are 2, 8, 20, 26, 48, 83, 88, 150, 850, 920,~1000 and 2300 nM for DNA-PK, p110 α , mTORC1, PI3KC2 β , p110 δ , mTORC2, p110 β , p110 γ , ATR, ATM, PI3KC2 α and hsVPS34 respectively). Inhibits growth of human tumor xenografts in mice in vivo . | [Description]
PI-103 (371935-74-9) is a potent inhibitor of PI-3 kinase, mTOR and DNA-PK, IC50 = 8, 88, 150, 48,? 20, 83 and 2 nM for p110α, p110?, p110γ, p110δ, mTORC1, mTORC2 and DNA-PK respectively.1,2 Synergizes with arsenic disulfide to eradicate AML stem cells by induction of differentiation.3 Inhibits the growth of gefitinib-resistant non-small cell lung cancer cell lines.4 Induces autophagy in drug-resistant glioma.5 Protects against a-synuclein-induced toxicity in human neurons by induction of macroautophagy.6 | [Uses]
PI 103 is a dual inhbitor of Class IA phosphatidylinositol 3-kinase and mammalian target of rapaymycin complex 1 (mTORC1), both of which are involved in pathways often activated in myelogenous leukemia. PI 103 also functions to enhance tumour radiosensitivity. | [Definition]
ChEBI: An organic heterotricyclic compound that is pyrido[3',2':4,5]furo[3,2-d]pyrimidine substituted at positions 2 and 4 by 3-hydroxyphenyl and morpholin-4-yl groups respectively. A dual-kinase inhibitor with anti-cancer properties. | [General Description]
A cell-permeable pyridinylfuranopyrimidine compound that acts as a potent and ATP-competitive inhibitor of DNA-PK, PI3-K, and mTOR (IC50 = 2, 8, 88, 48, 150, 26, 20, and 83 nM for DNA-PK, p110α, p110β, p110δ, p110γ, PI3-KC2β, mTORC1, and mTORC2, respectively). It inhibits ATR and ATM only at much higher concentrations (IC50 = 850 and 920 nM, respectively) and exhibits little activity towards a panel of more than 40 other kinases even at concentrations as high as 10 μM. Shown to effectively block PI3-K/Akt signaling and cell proliferation in glioma cell lines both in vitro and in vivo. A 10 mM (2 mg/574 μl) solution of PI-103 (Cat. No. 528101) in DMSO is also available. | [Biochem/physiol Actions]
Cell permeable: yes | [target]
Cell, 2013, 153(4):840-54 | [References]
Knight et al. (2006), A Pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling; Cell, 125 733
Raynaud et al. (2007), Pharmacologic characterization of a potent inhibitor of a class I phosphatidylinositide 3-kinases; Cancer Res., 67 5840
Hong et al. (2011), Arsenic disulfide synergizes with the phosphoinositide 3-kinase inhibitor PI-103 to eradicate acute myeloid leukemia stem cells by inducing differentiation; Carcinogenesis, 32 1550
Zou et al. (2009), A novel dual PI3Kalpha/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells; Int. J. Mol. Med. 24 97
Fan et al. (2010), Akt and autophagy cooperate to promote survival of drug-resistant glioma; Sci. Signal., 3 ra81
Hollerhage et al. (2019), Multiple molecular pathways stimulating macroautophagy protect from alpha-synuclein-induced toxicity in human neurons; Neuropharmacology, 149 13 |
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