CP-466722ATM inhibitor,potent and reversible CAS# 1080622-86-1 |
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1080622-86-1 | SDF | Download SDF |
| PubChem ID | 44551660 | Appearance | Powder |
| Formula | C17H15N7O2 | M.Wt | 349.35 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 7 mg/mL (20.04 mM; Need warming) | ||
| Chemical Name | 2-(6,7-dimethoxyquinazolin-4-yl)-5-pyridin-2-yl-1,2,4-triazol-3-amine | ||
| SMILES | COC1=C(C=C2C(=C1)C(=NC=N2)N3C(=NC(=N3)C4=CC=CC=N4)N)OC | ||
| Standard InChIKey | ILBRKJBKDGCSCB-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C17H15N7O2/c1-25-13-7-10-12(8-14(13)26-2)20-9-21-16(10)24-17(18)22-15(23-24)11-5-3-4-6-19-11/h3-9H,1-2H3,(H2,18,22,23) | ||
| 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 | CP-466722 is a potent and reversible ATM inhibitor. | |||||
| Targets | ATM | |||||
CP-466722 Dilution Calculator
CP-466722 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.8625 mL | 14.3123 mL | 28.6246 mL | 57.2492 mL | 71.5615 mL |
| 5 mM | 0.5725 mL | 2.8625 mL | 5.7249 mL | 11.4498 mL | 14.3123 mL |
| 10 mM | 0.2862 mL | 1.4312 mL | 2.8625 mL | 5.7249 mL | 7.1561 mL |
| 50 mM | 0.0572 mL | 0.2862 mL | 0.5725 mL | 1.145 mL | 1.4312 mL |
| 100 mM | 0.0286 mL | 0.1431 mL | 0.2862 mL | 0.5725 mL | 0.7156 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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CP-466722 is a selective inhibitor of ATM kinase with IC50 value of 0.41 μM [1].
ATM (ataxia-telangiectasia, mutated) is a serine/threonine protein kinase and plays an important role in the cellular responses to DNA double-strand breaks (DSBs) [2] [3].
CP-466722 is a potent ATM inhibitor and is regareded as a promising drug to increase tumor cells sensitivity to IR. When tested with MCF7 cells, CP-466722 (10 μM) showed inhibition on the pATM and pKAP1 signals which induced by etoposide pre-treatment (25 μM) [1]. In GBM 12 cells, CP-466722 treatment significantly increased the cell sensitivity to TMZ and increased the cell apoptosis which had no effect on the TMZ-resistant GBM12 TMZ cells which indicated that CP-466722 (as an ATM inhibitor) may enhance the efficacy of TMZ in tumors that were inherently sensitive to TMZ [2]. When tested with Hela, MCF-7 and mouse cells pre-treated with IR which induced the increase in ATM-dependent phosphorylation events and then CP-466722 treatment resulted in the disruption of ATM-dependent phosphorylation events and inhibiton of ATM-dependent p53 inducetion at the minimal dose of 6 μM. Further, it was shown that CP-466722 treatment disrupted ATM-dependent cell cycle in increasing the percent in G2/M phase while decreasing the proportion in G1-phase without adverse effects [3].
References:
[1]. Guo, K., et al., Development of a cell-based, high-throughput screening assay for ATM kinase inhibitors. J Biomol Screen, 2014. 19(4): p. 538-46.
[2]. Nadkarni, A., et al., ATM inhibitor KU-55933 increases the TMZ responsiveness of only inherently TMZ sensitive GBM cells. J Neurooncol, 2012. 110(3): p. 349-57.
[3]. Rainey, M.D., et al., Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation. Cancer Res, 2008. 68(18): p. 7466-74.
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GluA2-Containing AMPA Receptors Distinguish Ribbon-Associated from Ribbonless Afferent Contacts on Rat Cochlear Hair Cells.[Pubmed:27257620]
eNeuro. 2016 May 12;3(2). pii: eN-NWR-0078-16.
Mechanosensory hair cells release glutamate at ribbon synapses to excite postsynaptic afferent neurons, via AMPA-type ionotropic glutamate receptors (AMPARs). However, type II afferent neurons contacting outer hair cells in the mammalian cochlea were thought to differ in this respect, failing to show GluA immunolabeling and with many "ribbonless" afferent contacts. Here it is shown that antibodies to the AMPAR subunit GluA2 labeled afferent contacts below inner and outer hair cells in the rat cochlea, and that synaptic currents in type II afferents had AMPAR-specific pharmacology. Only half the postsynaptic densities of type II afferents that labeled for PSD-95, Shank, or Homer were associated with GluA2 immunopuncta or presynaptic ribbons, the "empty slots" corresponding to ribbonless contacts described previously. These results extend the universality of AMPAergic transmission by hair cells, and support the existence of silent afferent contacts.
Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation.[Pubmed:18794134]
Cancer Res. 2008 Sep 15;68(18):7466-74.
In response to DNA damage, the ATM protein kinase activates signal transduction pathways essential for coordinating cell cycle progression with DNA repair. In the human disease ataxia-telangiectasia, mutation of the ATM gene results in multiple cellular defects, including enhanced sensitivity to ionizing radiation (IR). This phenotype highlights ATM as a potential target for novel inhibitors that could be used to enhance tumor cell sensitivity to radiotherapy. A targeted compound library was screened for potential inhibitors of the ATM kinase, and CP466722 was identified. The compound is nontoxic and does not inhibit phosphatidylinositol 3-kinase (PI3K) or PI3K-like protein kinase family members in cells. CP466722 inhibited cellular ATM-dependent phosphorylation events and disruption of ATM function resulted in characteristic cell cycle checkpoint defects. Inhibition of cellular ATM kinase activity was rapidly and completely reversed by removing CP466722. Interestingly, clonogenic survival assays showed that transient inhibition of ATM is sufficient to sensitize cells to IR and suggests that therapeutic radiosensitization may only require ATM inhibition for short periods of time. The ability of CP466722 to rapidly and reversibly regulate ATM activity provides a new tool to ask questions about ATM function that could not easily be addressed using genetic models or RNA interference technologies.
ATM inhibitor KU-55933 increases the TMZ responsiveness of only inherently TMZ sensitive GBM cells.[Pubmed:23054561]
J Neurooncol. 2012 Dec;110(3):349-57.
Ataxia telangiectasia mutated (ATM) kinase is critical in sensing and repairing DNA double-stranded breaks (DSBs) such as those induced by temozolomide (TMZ). ATM deficiency increases TMZ sensitivity, which suggests that ATM inhibitors may be effective TMZ sensitizing agents. In this study, the TMZ sensitizing effects of 2 ATM specific inhibitors were studied in established and xenograft-derived glioblastoma (GBM) lines that are inherently sensitive to TMZ and derivative TMZ-resistant lines. In parental U251 and U87 glioma lines, the addition of KU-55933 to TMZ significantly increased cell killing compared to TMZ alone [U251 survival: 0.004 +/- 0.0015 vs. 0.08 +/- 0.01 (p < 0.001), respectively, and U87 survival: 0.02 +/- 0.005 vs. 0.04 +/- 0.002 (p < 0.001), respectively] and also elevated the fraction of cells arrested in G2/M [U251 G2/M fraction: 61.8 +/- 1.1 % vs. 35 +/- 0.8 % (p < 0.001), respectively, and U87 G2/M fraction 25 +/- 0.2 % vs.18.6 +/- 0.4 % (p < 0.001), respectively]. In contrast, KU-55933 did not sensitize the resistant lines to TMZ, and neither TMZ alone or combined with KU-55933 induced a G2/M arrest. While KU-55933 did not enhance TMZ induced Chk1/Chk2 activation, it increased TMZ-induced residual gamma-H2AX foci in the parental cells but not in the TMZ resistant cells. Similar sensitization was observed with either KU-55933 or CP-466722 combined with TMZ in GBM12 xenograft line but not in GBM12TMZ, which is resistant to TMZ due to MGMT overexpression. These findings are consistent with a model where ATM inhibition suppresses the repair of TMZ-induced DSBs in inherently TMZ-sensitive tumor lines, which suggests an ATM inhibitor potentially could be deployed with an improvement in the therapeutic window when combined with TMZ.
