PI-103
Synonym(s):3-(4-(4-Morpholinyl)pyrido[3ʹ,2ʹ:4,5]furo[3,2-d]pyrimidin-2-yl)phenol, mTOR Inhibitor V, PI 3-K Inhibitor V;PI-103 - CAS 371935-74-9 - Calbiochem
- CAS NO.:371935-74-9
- Empirical Formula: C19H16N4O3
- Molecular Weight: 348.36
- MDL number: MFCD11983145
- SAFETY DATA SHEET (SDS)
- Update Date: 2023-05-18 11:31:15
What is PI-103?
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
The Uses of PI-103
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.
What are the applications of Application
PI-103 is an ATP-competitive DNA-PK, PI 3-kinase, and FRAP inhibitor
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
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
Properties of PI-103
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. |
Safety information for PI-103
Computed Descriptors for PI-103
New Products
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