PI-103Class I PI3K, mTOR and DNA-PK inhibitor CAS# 371935-74-9 |
2D Structure
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Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
Cas No. | 371935-74-9 | SDF | Download SDF |
PubChem ID | 9884685 | Appearance | Powder |
Formula | C19H16N4O3 | M.Wt | 348.36 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : 25 mg/mL (71.76 mM; Need ultrasonic) | ||
Chemical Name | 3-(4-morpholin-4-ylpyrido[2,3]furo[2,4-b]pyrimidin-2-yl)phenol | ||
SMILES | C1COCCN1C2=NC(=NC3=C2OC4=C3C=CC=N4)C5=CC(=CC=C5)O | ||
Standard InChIKey | TUVCWJQQGGETHL-UHFFFAOYSA-N | ||
Standard 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 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | PI-103 is a multi-targeted inhibitor of PI3K for p110α/β/δ/γ with IC50 of 2 nM/3 nM/3 nM/15 nM, less potent to mTOR/DNA-PK with IC50 of 30 nM/23 nM. | |||||
Targets | Cell, 2013, 153(4):840-54 | p110β | p110δ | p110γ | mTOR | DNA-PK |
IC50 | 2 nM | 3 nM | 3 nM | 15 nM | 30 nM | 23 nM |
Cell experiment: [1] | |
Cell lines | A549 and H460 cells |
Preparation method | The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months. |
Reacting condition | 72 hours, 2 μM for A549 cells 0.5 μM for H460 cells |
Applications | Incubation of A549 cells with 2 μM PI-103 for 72 h induced an ~60% reduction in cell number. In contrast to A549 cells, H460 cells were highly sensitive to low-dose PI-103. Treatment of H460 cells with 0.5 μM PI-103 for 72 h resulted in ~60% inhibition. Results showed that exposure of A549 and H460 cells to PI-103 with the indicated concentrations for 72 h induced growth inhibition in a dose-dependent manner. |
Animal experiment: [2] | |
Animal models | FVB/N wild type mice injected with 37-31E-F3 cells |
Dosage form | Intraperitoneal injection, 10 mg/kg, daily |
Application | PI-103 treatment promoted a significant in vivo tumor growth compared with the DMSO treated mice. It was effective by partially inhibiting the Akt and S6 ribosomal protein phosphorylation. Tumors from PI-103-treated mice showed higher levels of cyclin D1 and more proliferating cells as indicated by the number of Ki67 positive cells. PI-103-treated tumors had the lowest apoptotic rate. |
Other notes | Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
References: [1] Zou Z Q, Zhang X H, Wang F, et al. A novel dual PI3Kalpha/mTOR inhibitor PI-103 with high antitumor activity in non-small cell lung cancer cells. Int J Mol Med, 2009, 24(1): 97-101. [2] López‐Fauqued M, Gil R, Grueso J, et al. The dual PI3K/mTOR inhibitor PI‐103 promotes immunosuppression, in vivo tumor growth and increases survival of sorafenib-treated melanoma cells. International journal of cancer, 2010, 126(7): 1549-1561. |
PI-103 Dilution Calculator
PI-103 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.8706 mL | 14.353 mL | 28.7059 mL | 57.4119 mL | 71.7648 mL |
5 mM | 0.5741 mL | 2.8706 mL | 5.7412 mL | 11.4824 mL | 14.353 mL |
10 mM | 0.2871 mL | 1.4353 mL | 2.8706 mL | 5.7412 mL | 7.1765 mL |
50 mM | 0.0574 mL | 0.2871 mL | 0.5741 mL | 1.1482 mL | 1.4353 mL |
100 mM | 0.0287 mL | 0.1435 mL | 0.2871 mL | 0.5741 mL | 0.7176 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Abstract
PI-103 is a PI3K/Akt/mTOR signaling pathway inhibitor that induces apoptosis in LSCs. The combination of PI-103 and DNR synergistically induces apoptosis in LSCs without affecting hematopoietic stem cells, where PI-103 sensitizes LSCs to DNR-induced cytotoxicity.
Abstract
The co-treatment of PI103, a PI3K/mTOR inhibitor, and CQ induces lysosome-mediated apoptosis in lung carcinoma cells, where PI103 increases lysosomal volume and function with its resistance reduced by CQ.
Abstract
Propidium iodide-103 not only effectively inhibited PI3K/AKT/mTOR pathway activated by As(2)S(2) but also synergized with As(2)S(2) to eradicate non-APL LSCs, promote their differentiation and reduce their repopulation.
Abstract
PI-103 is a PI3-kinase/mTOR inhibitor that exhibits anti-glioma activity through inhibiting tumor cell proliferation and invasion, arresting G(0)-G(1) phases of cell cycle and attenuating tumor growth. The combined therapy of PI-103 and S-TRAIL showed enhanced tumor volume reduction.
Abstract
The anti-proliferative activities of sorafenib, PI-103 and their combination in Huh7 have been demonstrated.
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The University of Tokyo
Korea University
PI-103 is a potent and selective inhibitor of class I PI3K, mTOR and DNA-PK with IC50 values of 2, 3, 3, 15, 30 and 23 nM for p110α, p110β, p110δ, p110γ, mTOR and DNA-PK, respectively [1].
PI-103 showed potent antiproliferation activities in various cancer cell lines such as prostate, ovary and glioblastoma. It exerted GI50 values of 0.14, 0.06, 0.13, 0.10, 0.12 and 0.08 μM in U87MG, IGROV-1, DETROIT-562, PC3, SKOV-3 and HUVEC cells, respectively. In U87MG cells, 2 hour-treatment of PI-103 caused inhibition effects on various phosphorylated protein biomarkers of PI3K pathway with IC50 values of 15, 36, 111, 106 and 105 nM for p-AKTSer473, p-AKTThr308, p-GSK3βSer9, p-p70S6KThr421/Ser424 and p-S6RPSer235/Ser236, respectively [1].
References:
[1] Raynaud F I, Eccles S A, Patel S, et al. Biological properties of potent inhibitors of class I phosphatidylinositide 3-kinases: from PI-103 through PI-540, PI-620 to the oral agent GDC-0941. Molecular cancer therapeutics, 2009, 8(7): 1725-1738.
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PI-103 attenuates PI3K-AKT signaling and induces apoptosis in murineT-cell lymphoma.[Pubmed:27658642]
Leuk Lymphoma. 2017 May;58(5):1153-1161.
Aberrant activation of PI3K-AKT signaling in many pathological conditions including cancer has attracted much of interest for drug targeting. Various isoforms are known from three classes of PI3K. Targeting selective isoform is advantageous to overcome the global deleterious effects of drug. PI-103 is a specific inhibitor of p110alpha of class I PI3K. The present study is aimed to analyze anti-carcinogenic activity of PI-103 in Dalton's lymphoma ascite (DLA) cells. Result shows regression in cell proliferation and increased apoptosis in terms of increased Annexin V binding, nuclear fragmentation and active caspase 3 level. It is correlated with attenuation of PI3K-AKT signaling by PI-103 via downregulation of the level of p110alpha, phospho-p85alpha, phospho- AKT, and PKCalpha in DLA cells as well as in H2O2 induced DLA cells. Additionally, ROS accumulation is declined in H2O2 induced DLA cells. Overall result suggests that PI-103 attenuates PI3K-AKT signaling via induction of apoptosis in murine T-cell lymphoma.
[A dual PI3K/mTOR inhibitor, PI-103, cooperates with TRAIL in laryngeal squamous carcinoma cells in vitro].[Pubmed:27464548]
Zhonghua Yi Xue Za Zhi. 2016 Jul 19;96(27):2187-91.
OBJECTIVE: To investigate the effects of a dual phosphoinosmde-3-kinase (PI3K)/ mammalian target of rapamycin (mTOR) inhibitor, PI-103, cooperating with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the laryngeal squamous carcinoma Hep-2 cells. METHODS: Hep-2 cells were divided into 7 groups: LY294002 group, Rapamycin group, PI-103 group, LY294002+ TRAIL group, Rapamycin+ TRAIL group, PI-103+ TRAIL group and control group.The cell cycle and apoptosis of Hep-2 cells were assessed by flow cytometry.For PI-103 group, PI-103+ TRAIL group and control group, migration and invasion ability were measured by transwell migration and invasion assay respectively.The expression of relative proteins in apoptosis and PI3K/AKT/mTOR signal pathway was examined by Western blotting. RESULTS: Combination of PI-103 and TRAIL could make cell cycle arrest at S phase (G1: 1.80%+/-0.30%; G2: 0.00), inhibit cell proliferation, and enhance apoptosis (66.78%+/-2.93%) (P<0.05). Combination of PI-103 and TRAIL could statistically decrease the migration and invasion number of Hep-2 cells (17.0+/-3.4, 18.4+/-5.4) than that of PI-103 group (41.2+/-3.8, 41.6+/-4.7). PI-103 could inhibit PI3K/AKT/mTOR signal pathway by decreasing the protein expression of p-AKT and p-4E-BP1.Comparing with the control group, the expression of cysteinyl aspartate specific proteinase (Caspase) 9, 8, 3 were increased while the expression of Cyclin D1, Cyclin E1, p-AKT, p-4E-BP1 were decreased in PI-103 and PI-103+ TRAIL group (P<0.05). CONCLUSION: Enhanced anti-tumor effects was observed by combination of PI-103 and TRAIL on laryngeal cancer cells in vitro and this combined administration might be a promising strategy for clinical treatment of laryngeal cancer.
Dual PI3K- and mTOR-inhibitor PI-103 can either enhance or reduce the radiosensitizing effect of the Hsp90 inhibitor NVP-AUY922 in tumor cells: The role of drug-irradiation schedule.[Pubmed:27224913]
Oncotarget. 2016 Jun 21;7(25):38191-38209.
Inhibition of Hsp90 can increase the radiosensitivity of tumor cells. However, inhibition of Hsp90 alone induces the anti-apoptotic Hsp70 and thereby decreases radiosensitivity. Therefore, preventing Hsp70 induction can be a promising strategy for radiosensitization. PI-103, an inhibitor of PI3K and mTOR, has previously been shown to suppress the up-regulation of Hsp70. Here, we explore the impact of combining PI-103 with the Hsp90 inhibitor NVP-AUY922 in irradiated glioblastoma and colon carcinoma cells. We analyzed the cellular response to drug-irradiation treatments by colony-forming assay, expression of several marker proteins, cell cycle progression and induction/repair of DNA damage. Although PI-103, given 24 h prior to irradiation, slightly suppressed the NVP-AUY922-mediated up-regulation of Hsp70, it did not cause radiosensitization and even diminished the radiosensitizing effect of NVP-AUY922. This result can be explained by the activation of PI3K and ERK pathways along with G1-arrest at the time of irradiation. In sharp contrast, PI-103 not only exerted a radiosensitizing effect but also strongly enhanced the radiosensitization by NVP-AUY922 when both inhibitors were added 3 h before irradiation and kept in culture for 24 h. Possible reasons for the observed radiosensitization under this drug-irradiation schedule may be a down-regulation of PI3K and ERK pathways during or directly after irradiation, increased residual DNA damage and strong G2/M arrest 24 h thereafter. We conclude that duration of drug treatment before irradiation plays a key role in the concomitant targeting of PI3K/mTOR and Hsp90 in tumor cells.
PI-103 and Quercetin Attenuate PI3K-AKT Signaling Pathway in T- Cell Lymphoma Exposed to Hydrogen Peroxide.[Pubmed:27494022]
PLoS One. 2016 Aug 5;11(8):e0160686.
Phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT) pathway has been considered as major drug target site due to its frequent activation in cancer. AKT regulates the activity of various targets to promote tumorigenesis and metastasis. Accumulation of reactive oxygen species (ROS) has been linked to oxidative stress and regulation of signaling pathways for metabolic adaptation of tumor microenvironment. Hydrogen peroxide (H2O2) in this context is used as ROS source for oxidative stress preconditioning. Antioxidants are commonly considered to be beneficial to reduce detrimental effects of ROS and are recommended as dietary supplements. Quercetin, a ubiquitous bioactive flavonoid is a dietary component which has attracted much of interest due to its potential health-promoting effects. Present study is aimed to analyze PI3K-AKT signaling pathway in H2O2 exposed Dalton's lymphoma ascite (DLA) cells. Further, regulation of PI3K-AKT pathway by quercetin as well as PI-103, an inhibitor of PI3K was analyzed. Exposure of H2O2 (1mM H2O2 for 30min) to DLA cells caused ROS accumulation and resulted in increased phosphorylation of PI3K and downstream proteins PDK1 and AKT (Ser-473 and Thr-308), cell survival factors BAD and ERK1/2, as well as TNFR1. However, level of tumor suppressor PTEN was declined. Both PI-103 & quercetin suppressed the enhanced level of ROS and significantly down-regulated phosphorylation of AKT, PDK1, BAD and level of TNFR1 as well as increased the level of PTEN in H2O2 induced lymphoma cells. The overall result suggests that quercetin and PI3K inhibitor PI-103 attenuate PI3K-AKT pathway in a similar mechanism.