PIK-90PI3K inhibitor,potent selective CAS# 677338-12-4 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 677338-12-4 | SDF | Download SDF |
PubChem ID | 6857685 | Appearance | Powder |
Formula | C18H17N5O3 | M.Wt | 351.36 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Solubility | DMSO : 1.75 mg/mL (4.98 mM; Need ultrasonic and warming) | ||
Chemical Name | N-(7,8-dimethoxy-2,3-dihydroimidazo[1,2-c]quinazolin-5-yl)pyridine-3-carboxamide | ||
SMILES | COC1=C(C2=C(C=C1)C3=NCCN3C(=N2)NC(=O)C4=CN=CC=C4)OC | ||
Standard InChIKey | ZJAVHOMVDCMAMF-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C18H17N5O3/c1-25-13-6-5-12-14(15(13)26-2)21-18(23-9-8-20-16(12)23)22-17(24)11-4-3-7-19-10-11/h3-7,10H,8-9H2,1-2H3,(H,21,22,24) | ||
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 | PIK-90 is a potent and cell-permeable inhibitor of PI3K with IC50 values of 11 nM, 350 nM, 18 nM and 58 nM for p110α, p110β, p110γ and p110δ, respectively. | ||||||
Targets | p110α | p110β | p110γ | p110δ | |||
IC50 | 11 nM | 350 nM | 18 nM | 58 nM |
PIK-90 Dilution Calculator
PIK-90 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.8461 mL | 14.2304 mL | 28.4608 mL | 56.9217 mL | 71.1521 mL |
5 mM | 0.5692 mL | 2.8461 mL | 5.6922 mL | 11.3843 mL | 14.2304 mL |
10 mM | 0.2846 mL | 1.423 mL | 2.8461 mL | 5.6922 mL | 7.1152 mL |
50 mM | 0.0569 mL | 0.2846 mL | 0.5692 mL | 1.1384 mL | 1.423 mL |
100 mM | 0.0285 mL | 0.1423 mL | 0.2846 mL | 0.5692 mL | 0.7115 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. |
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PIK-90 is a broad-spectrum PI3K inhibitors that inhibits PI3Kα, PI3Kγ and PI3Kδ with IC50 values of 11, 18 and 58nM, respectively [1].
Studies showed that PIK-90 induced increased levels of secreted IgE at 1 μmol/L, while it inhibited IgE production at doses of greater than 2 μmol/L [2]. PIk-90 has been reported to block Akt phosphorylation. PIK-90 combined with the CDK2 inhibitor has been demonstrated to induce apoptosis in LN229 PTENWT cells. In addition, PIK-90 combined with siRNA against both CDK1 and CDK2 has shown to induce cell death, whereas PIK-90 combined with siRNA against CDK1 or CDK2 had no apoptotic effect [3].
In vivo, PIK-90 combined with roscovitine revealed a significant reduction of tumor size in nude mice implanted with GBM43 cells [3].
References:
[1] Van Keymeulen A1, Wong K, Knight ZA, Govaerts C, Hahn KM, Shokat KM, Bourne HR. To stabilize neutrophil polarity, PIP3 and Cdc42 augment RhoA activity at the back as well as signals at the front. J Cell Biol. 2006 Jul 31;174(3):437-45. Epub 2006 Jul 24.
[2] Zhang TT1, Okkenhaug K, Nashed BF, Puri KD, Knight ZA, Shokat KM, Vanhaesebroeck B, Marshall AJ. Genetic or pharmaceutical blockade of p110delta phosphoinositide 3-kinase enhances IgE production. J Allergy Clin Immunol. 2008 Oct;122(4):811-819.e2.
[3] Cheng CK1, Gustafson WC, Charron E, Houseman BT, Zunder E, Goga A, Gray NS, Pollok B, Oakes SA, James CD, Shokat KM, Weiss WA, Fan QW. Dual blockade of lipid and cyclin-dependent kinases induces synthetic lethality in malignant glioma. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12722-7.
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A dual phosphoinositide-3-kinase alpha/mTOR inhibitor cooperates with blockade of epidermal growth factor receptor in PTEN-mutant glioma.[Pubmed:17804702]
Cancer Res. 2007 Sep 1;67(17):7960-5.
We have shown previously that blockade of epidermal growth factor receptor (EGFR) cooperates with a pan-selective inhibitor of phosphoinositide-3-kinase (PI3K) in EGFR-driven glioma. In this communication, we tested EGFR-driven glioma differing in PTEN status, treating with the EGFR inhibitor erlotinib and a novel dual inhibitor of PI3Kalpha and mTOR (PI-103). Erlotinib blocked proliferation only in PTEN(wt) cells expressing EGFR. Although erlotinib monotherapy showed little effect in PTEN(mt) glioma, PI-103 greatly augmented the antiproliferative efficacy of erlotinib in this setting. To address the importance of PI3K blockade, we showed in PTEN(mt) glioma that combining PI-103 and erlotinib was superior to either monotherapy or to therapy combining erlotinib with either rapamycin (an inhibitor of mTOR) or PIK-90 (an inhibitor of PI3Kalpha). These experiments show that a dual inhibitor of PI3Kalpha and mTOR augments the activity of EGFR blockade, offering a mechanistic rationale for targeting EGFR, PI3Kalpha, and mTOR in the treatment of EGFR-driven, PTEN-mutant glioma.
Dual blockade of lipid and cyclin-dependent kinases induces synthetic lethality in malignant glioma.[Pubmed:22802621]
Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12722-7.
Malignant glioma, the most common primary brain tumor, is generally incurable. Although phosphatidylinositol-3-kinase (PI3K) signaling features prominently in glioma, inhibitors generally block proliferation rather than induce apoptosis. Starting with an inhibitor of both lipid and protein kinases that induced prominent apoptosis and that failed early clinical development because of its broad target profile and overall toxicity, we identified protein kinase targets, the blockade of which showed selective synthetic lethality when combined with PI3K inhibitors. Prioritizing protein kinase targets for which there are clinical inhibitors, we demonstrate that cyclin-dependent kinase (CDK)1/2 inhibitors, siRNAs against CDK1/2, and the clinical CDK1/2 inhibitor roscovitine all cooperated with the PI3K inhibitor PIK-90, blocking the antiapoptotic protein Survivin and driving cell death. In addition, overexpression of CDKs partially blocked some of the apoptosis caused by PIK-75. Roscovitine and PIK-90, in combination, were well tolerated in vivo and acted in a synthetic-lethal manner to induce apoptosis in human glioblastoma xenografts. We also tested clinical Akt and CDK inhibitors, demonstrating induction of apoptosis in vitro and providing a preclinical rationale to test this combination therapy in patients.
Isoform-selective phosphoinositide 3'-kinase inhibitors inhibit CXCR4 signaling and overcome stromal cell-mediated drug resistance in chronic lymphocytic leukemia: a novel therapeutic approach.[Pubmed:19318683]
Blood. 2009 May 28;113(22):5549-57.
Phosphoinositide 3-kinases (PI3Ks) are among the most frequently activated signaling pathways in cancer. In chronic lymphocytic leukemia (CLL), signals from the microenvironment are critical for expansion of the malignant B cells, and cause constitutive activation of PI3Ks. CXCR4 is a key receptor for CLL cell migration and adhesion to marrow stromal cells (MSCs). Because of the importance of CXCR4 and PI3Ks for CLL-microenvironment cross-talk, we investigated the activity of novel, isoform-selective PI3K inhibitors that target different isoforms of the p110-kDa subunit. Inhibition with p110alpha inhibitors (PIK-90 and PI-103) resulted in a significant reduction of chemotaxis and actin polymerization to CXCL12 and reduced migration beneath MSC (pseudoemperipolesis). Western blot and reverse phase protein array analyses consistently demonstrated that PIK-90 and PI-103 inhibited phosphorylation of Akt and S6, whereas p110delta or p110beta/p110delta inhibitors were less effective. In suspension and MSC cocultures, PI-103 and PIK-90 were potent inducers of CLL cell apoptosis. Moreover, these p110alpha inhibitors enhanced the cytotoxicity of fludarabine and reversed the protective effect of MSC on fludarabine-induced apoptosis. Collectively, our data demonstrate that p110alpha inhibitors antagonize stromal cell-derived migration, survival, and drug-resistance signals and therefore provide a rational to explore the therapeutic activity of these promising agents in CLL.