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| Product Name: | PI-103 | | Synonyms: | Phenol, 3-[4-(4-Morpholinyl)pyrido[3',2':4,5]furo[3,2-d]pyriMidin-2-yl]-;3-(4-Morpholinopyrido[3',2':4,5]
furo[3,2-d]pyriMidin-2-yl)phenol;PI 3-Kinase Inhibitor (PI-103) B-0303;PI-103, Free Base, >99%;PI-103 - CAS 371935-74-9 - Calbiochem;PI-103HydrochlorideSalt;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 | | CAS: | 371935-74-9 | | MF: | C19H16N4O3 | | MW: | 348.36 | | EINECS: | | | Product Categories: | Akt;mTOR;Inhibitors;PI3K | | Mol File: | 371935-74-9.mol |  |
| | PI-103 Chemical Properties |
| density | 1.409±0.06 g/cm3(Predicted) | | storage temp. | Keep in dark place,Sealed in dry,Store in freezer, under -20°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. |
| | PI-103 Usage And Synthesis |
| 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. | | 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 . | | 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 |
| | PI-103 Preparation Products And Raw materials |
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