1、CID755673Cat. No.: HY-12239CAS No.: 521937-07-5Molecular Formula: CHNOMolecular Weight: 217.22Target: PKDPathway: ApoptosisStorage: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 monthSolvent PKD3, IC50: 227 nM; PKD2, IC50: 280 nMIn Vitro CID755673 exhibits selective PKD1 inhibition whe
2、n compared with AKT, polo-like kinase 1 (PLK1), CDK activating kinase (CAK), CAMKII, and three different PKC isoforms. It is not competitive with ATP for enzyme inhibition. CID755673 blocks phorbol ester-induced endogenous PKD1 activation in LNCaP cells in a concentration-dependent manner. CID755673
3、 inhibitS the known biological actions of PKD1 including phorbol ester-induced class IIa histone deacetylase 5 nuclear exclusion, vesicular stomatitis virus glycoprotein transport from the Golgi to the plasma membrane, and the ilimaquinone-induced Golgi fragmentation. CID755673 inhibits prostate can
4、cer cell proliferation, cell migration, and invasion1.Product Data Sheet InhibitorsAgonistsScreening Librarieswww.MedChemE1In Vivo Acute administration of the PKD inhibitor CID755673 to normal mice reduces both PKD1 and 2 phosphorylation in a time and dose-dependent manner. Chronic CID755673 adminis
5、tration to T2D db/db mice for two weeks reduces expression of the gene expression signature of PKD activation, enhances indices of both diastolic and systolic left ventricular function and is associated with reduced heart weight2.PROTOCOLKinase Assay 1 The radiometric kinase assay is carried out by
6、coincubating 0.5 Ci of -32PATP, 20 M ATP, 50 ng of purified recombinant human PKD (PKD1, PKD2, and PKD3) or CAMKII proteins, and 2.5 g of Syntide-2 in 50 L of kinase buffer that contains 50 mM Tris-HCl, pH 7.5, 4 mM MgCl2, 10 mM -mercaptoethanol. The reaction is carried out under conditions that the
7、 initial rate is within the linear kinetic range1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 The wound-induced migration is triggered by scraping the cells with a plastic pipette tip, and the wound is imaged immediately. The DU145 cell
8、s are then are treated with or without CID755673 at different concentrations. The wound is imaged immediately (0 h) and at different intervals with an inverted phase-contrast microscope with a 10 objective. At the end of the assay, cells are fixed with methanol and stained with crystal violet for a
9、final image1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Administration 2Mice: For acute inhibitor studies, C57BL6 mice are administered a single dose of vehicle (5% DMSO in PBS, pH 7.4), or the selective PKD inhibitor CID755673 at 1 or 10mg/
10、kg body weight. Mice are killed one or four hr later and heart collected for later analysis. For chronic inhibitor experiments, 8-week old db/db mice receives vehicle or CID755673 at 1 or 10mg/kg bodyweight for 16 days, by daily intraperitoneal (i.p.) injection2.MCE has not independently confirmed t
11、he accuracy of these methods. They are for reference only.CUSTOMER VALIDATIONSee more customer validations on www.MedChemEREFERENCES1. Sharlow ER, et al. Potent and selective disruption of protein kinase D functionality by a benzoxoloazepinolone. J Biol Chem. 2008 Nov 28;283(48):33516-26.2. Venardos
12、 K, et al. The PKD inhibitor CID755673 enhances cardiac function in diabetic db/db mice. PLoS One. 2015 Mar 23;10(3):e0120934.3. YangLei, et al. Regulation of protein kinase D1 on the expression of eNOS and Ang1 in myocardium of rats with myocardial infartion. Journal of Jinan University (Natural Sc
13、ience 10(7):10528-10534 Chinese Journal of Pathophysiology. 2016null32(1):146-150null155. Journal of Jinan University (Natural Science & Medicine Edition). 2015 Dec 36 (6). Harvard Medical School LINCS LIBRARYwww.MedChemE2Caution: Product has not been fully validated for medical applications. For re
14、search Inhibitors, Agonists, Screening Librarieswww.MedChemESafety Data SheetRevision Date:Oct.-10-2018Print Date: Oct.-10-20181. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name : CID755673Catalog No. : HY-12239CAS No. : 521937-07-51.2 Relevant identified uses of the substance o
15、r mixture and uses advised againstIdentified uses : Laboratory 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 IDENTIF
16、ICATION2.1 Classification of the substance or mixtureGHS 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 statementsPictogram
17、Signal word WarningHazard statement(s)H302 Harmful if 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 SW
18、ALLOWED: Call a POISON CENTER or doctor physician if 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: NoneFormul
19、a: C12H11NO3Molecular Weight: 217.22CAS No. : 521937-07-54. 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
20、 call a physician.Skin contactRinse skin thoroughly 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 resusci
21、tation.IngestionWash out mouth with water; Do NOT induce 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 spec
22、ial treatment neededTreat symptomatically.5. FIRE FIGHTING 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 Advi
23、ce for firefightersWear self-contained breathing apparatus 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. Evac
24、uate personnelto safe areas.Refer to protective measures 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 liq
25、uid-binding material (diatomite, universal binders); 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. A
26、void dust and aerosol formation. Use only in areas 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:P
27、owder-20C 3 years4C 2 yearsIn solvent-80C 6 months-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
28、occupational exposure limit values.8.2 Exposure controlsEngineering 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 Imper
29、vious clothing.Respiratory protection Suitable respirator.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 propertiesAppearan
30、ce White to off-white (Solid)Odor No data availableOdor 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 availableVapor pressure No data avai
