1、GSK1059615Cat. No.: HY-12036CAS No.: 958852-01-2Molecular Formula: CHNOSMolecular Weight: 333.36Target: PI3K; mTORPathway: PI3K/Akt/mTORStorage: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 monthSolvent PI3K, IC50: 0.6 nM; PI3K, IC50: 5 nM; PI3K, IC50: 2 nM; mTOR, IC50: 12 nMIn Vitro
2、GSK1059615 inhibits PI3K, , and , with Ki of 0.42 nM, 0.6 nM, 0.47 nM and 1.7 nM, respectively1. In T47D and BT474 cancer cells, GSK1059615 inhibits the phosphorylation of Akt at S473, with IC50 of 40 nM2.In Vivo GSK1059615 (25 mg/kg) effectively inhibits tumor growth in xenograft mice models of BT4
3、74 or HCC1954 breast cancer cells1.Product Data Sheet InhibitorsAgonistsScreening Librarieswww.MedChemE1PROTOCOLKinase Assay 2 The measurement of the GSK1059615-dependent inhibition of the PI3Ks is accessed using a HTRF based PI3K profiling assay kit. 400 pM enzyme is used in PI3K and assays, 200 pM
4、 in PI3K assays, and 1 nM in PI3K assay. In addition, the PI3K, , and assays are run with 150 mM NaCl and 100 M ATP, while the PI3K assay is run with no NaCl and 15 M ATP. All reactions are run at 10 M PIP2. GSK1059615 is serially diluted (3-fold in DMSO), and 50 nL is transferred to a 384-well low-
5、volume assay plate. PI3K Reaction Buffer is prepared by diluting the stock 1:4 with de-ionized water. Freshly prepared DTT is added at a final concentration of 5 mM on the day of use. Enzyme addition and GSK1059615 pre-incubation are initiated by the addition of 2.5 L of PI3K in reaction buffer. Pla
6、tes are incubated at room temperature for 15 min. Reactions are initiated by addition of 2.5 L of 2 substrate solution (PIP2 and ATP in 1 reaction buffer). Plates are incubated at room temperature for one hour. Reactions are quenched by the addition of 2.5 L of stop solution. The quenched reactions
7、are then processed to detect product formation by adding 2.5 L of Detection Solution. Following a 1-hour incubation in the dark, the HTRF signal is measured on the Envision plate reader set for 330 nm excitation and dual emission detection at 620 nm (Eu) and 665 nm (APC). The IC50 value is then obta
8、ined.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 2 Cells are plate at a density of 1104 cells per well in clear flat-bottomed 96-well plates and incubated overnight. Then, GSK1059615 is added and the plates are incubated for 30 min. At th
9、e end of incubation, media is aspirated from the plates, and the plate is wash once with cold PBS. 80 L MSD Lysis buffer is added into each well and the plates are incubated on a shaker at 4C for at least 30 min. For Akt duplex assay, plates are washed with 200 L/well wash buffer for 4 times and tap
10、ped on paper towel to blot. Then, 60 L lysates is added to each well and the plates are incubated on shaker at room temperature for 1 hour. After another 4 times washing, antibody is added (25 L per well) and the plates are incubated on shaker for 1 hour and washed again. Finally, Read Buffer is add
11、ed (150 L per well) and the plates are read immediately. IC50 values are then obtained.MCE has not independently confirmed the accuracy of these methods. They are for reference only.CUSTOMER VALIDATIONSee more customer validations on www.MedChemEREFERENCES1. Carnero A. Novel inhibitors of the PI3K f
12、amily. Expert Opin Investig Drugs. 2009 Sep;18(9):1265-77.2. Maira SM, et al. From the bench to the bed side: PI3K pathway inhibitors in clinical development. Curr Top Microbiol Immunol, 2010, 347, 209-239.3. Takashi Kei Kishimoto, et al. Methods and compositions for attenuating gene therapy anti-vi
13、ral transfer vector immune responses. US 20160074531 A1. Patent. US10046064B2. Patent. US20180193482A1. Patent. US20160074531A1. Patent. US20160074372A1. Patent. US20160074532A1.www.MedChemE2Caution: Product has not been fully validated for medical app Inhibitors, Agonists, Screening Librarieswww.Me
14、dChemESafety Data SheetRevision Date:Oct.-08-2018Print Date: Oct.-08-20181. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name : GSK1059615Catalog No. : HY-12036CAS No. : 958852-01-21.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses : L
15、aboratory chemicals, manufacture of substances.1.3 Details of the supplier of the safety data sheetCompany: MedChemExpress USATel: 609-228-6898Fax: 609-228-5909E-mail: 1.4 Emergency telephone numberEmergency Phone #: 609-228-68982. HAZARDS IDENTIFICATION2.1 Classification of the substance or mixture
16、GHS Classification in accordance with 29 CFR 1910 (OSHA HCS)Acute toxicity, Oral (Category 4),H302Acute aquatic toxicity (Category 1),H400Chronic aquatic toxicity (Category 1),H4102.2 GHS Label elements, including precautionary statementsPictogramSignal word WarningHazard statement(s)H302 Harmful if
17、 swallowed.H410 Very toxic to aquatic life with long lasting effects.Precautionary statement(s)P264 Wash skin thoroughly after handling.P270 Do not eat, drink or smoke when using this product.P273 Avoid release to the environment.P301 + P312 IF SWALLOWED: Call a POISON CENTER or doctor physician if
18、you feel unwell.P330 Rinse mouth.P391 Collect spillage.P501 Dispose of contents container to an approved waste disposal plant.2.3 Other hazardsPage 1 of 6 www.MedChemENone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms: NoneFormula: C18H11N3O2SMolecular Weight: 333.36CAS No. : 95885
19、2-01-24. FIRST AID MEASURES4.1 Description of first aid measuresEye contactRemove any contact lenses, locate eye-wash station, and flush eyes immediately with large amounts of water. Separate eyelidswith fingers to ensure adequate flushing. Promptly call a physician.Skin contactRinse skin thoroughly
20、 with large amounts of water. Remove contaminated clothing and shoes and call a physician.InhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-to-mouth resuscitation.IngestionWash out mouth with water; Do NOT i
21、nduce vomiting; call a physician.4.2 Most important symptoms and effects, both acute and delayedThe most important known symptoms and effects are described in the labelling (see section 2.2).4.3 Indication of any immediate medical attention and special treatment neededTreat symptomatically.5. FIRE F
22、IGHTING MEASURES5.1 Extinguishing mediaSuitable extinguishing mediaUse water spray, dry chemical, foam, and carbon dioxide fire extinguisher.5.2 Special hazards arising from the substance or mixtureDuring combustion, may emit irritant fumes.5.3 Advice for firefightersWear self-contained breathing ap
23、paratus and protective clothing.6. ACCIDENTAL RELEASE MEASURES6.1 Personal precautions, protective equipment and emergency proceduresUse full personal protective equipment. Avoid breathing vapors, mist, dust or gas. Ensure adequate ventilation. Evacuate personnelto safe areas.Refer to protective mea
24、sures listed in sections 8.6.2 Environmental precautionsTry to prevent further leakage or spillage. Keep the product away from drains or water courses.6.3 Methods and materials for containment and cleaning upAbsorb solutions with finely-powdered liquid-binding material (diatomite, universal binders)
25、; Decontaminate surfaces andequipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.Page 2 of 6 www.MedChemE7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust and aerosol formation. Use only in areas
26、with appropriate exhaustventilation.7.2 Conditions for safe storage, including any incompatibilitiesKeep container tightly sealed in cool, well-ventilated area. Keep away from direct sunlight and sources of ignition.Recommended storage temperature:Powder-20C 3 years4C 2 yearsIn solvent-80C 6 months-
27、20C 1 monthShipping at room temperature if less than 2 weeks.7.3 Specific end use(s)No data available.8. EXPOSURE CONTROLS/PERSONAL PROTECTION8.1 Control parametersComponents with workplace control parametersThis product contains no substances with occupational exposure limit values.8.2 Exposure con
28、trolsEngineering controlsEnsure adequate ventilation. Provide accessible safety shower and eye wash station.Personal protective equipmentEye protection Safety goggles with side-shields.Hand protection Protective gloves.Skin and body protection Impervious clothing.Respiratory protection Suitable resp
29、irator.Environmental exposure controlsKeep the product away from drains, water courses or the soil. Cleanspillages in a safe way as soon as possible.9. PHYSICAL AND CHEMICAL PROPERTIES9.1 Information on basic physical and chemical propertiesAppearance Light yellow to yellow (Solid)Odor No data avail
30、ableOdor threshold No data availablepH No data availableMelting/freezing point No data availableBoiling point/range No data availableFlash point No data availableEvaporation rate No data availableFlammability (solid, gas) No data availableUpper/lower flammability or explosive limitsNo data available
31、Vapor pressure No data availableVapor density No data availableRelative density No data availablePage 3 of 6 www.MedChemEWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition temperature No data availableViscosity No data av
32、ailableExplosive properties No data availableOxidizing properties No data available9.2 Other safety informationNo data available.10. STABILITY AND REACTIVITY10.1 ReactivityNo data available.10.2 Chemical stabilityStable under recommended storage conditions.10.3 Possibility of hazardous reactionsNo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, stro
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