1、 Inhibitors, Agonists, Screening Librarieswww.MedChemESafety Data SheetRevision Date:Nov.-02-2017Print Date: Nov.-02-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name : SAR7334Catalog No. : HY-15699CAS No. : 1333210-07-31.2 Relevant identified uses of the substance or mixtu
2、re 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 IDENTIFICATION
3、2.1 Classification of the substance or mixtureNot a hazardous substance or mixture.2.2 GHS Label elements, including precautionary statementsNot a hazardous substance or mixture.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms: SAR 7334; SAR7334Formula: C21H22ClN
4、3OMolecular Weight: 367.87CAS No. : 1333210-07-34. 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 p
5、hysician.Skin contactRinse skin thoroughly with large amounts of water. Remove contaminated clothing and shoes and call a physician.Page 1 of 5 www.MedChemEInhalationImmediately relocate self or casualty to fresh air. If breathing is difficult, give cardiopulmonary resuscitation (CPR). Avoid mouth-t
6、o-mouth resuscitation.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 att
7、ention and special 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
8、 fumes.5.3 Advice 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 ve
9、ntilation. Evacuate 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 fine
10、ly-powdered liquid-binding material (diatomite, universal binders); Decontaminate surfaces andequipment by scrubbing with alcohol; Dispose of contaminated material according to Section 13.7. HANDLING AND STORAGE7.1 Precautions for safe handlingAvoid inhalation, contact with eyes and skin. Avoid dust
11、 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:Powder-20C
12、 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 parametersPage 2 of 5 www.MedChemEComponents with workplace control parametersThis product contains no s
13、ubstances with 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 p
14、rotection Impervious 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 pro
15、pertiesAppearance Light yellow to yellow (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 avai
16、lableUpper/lower flammability or explosive limitsNo data availableVapor pressure No data availableVapor density No data availableRelative density No data availableWater Solubility No data availablePartition coefficient No data availableAuto-ignition temperature No data availableDecomposition tempera
17、ture No data availableViscosity No data availableExplosive 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.1
18、0.3 Possibility of hazardous reactionsPage 3 of 5 www.MedChemENo data available.10.4 Conditions to avoidNo data available.10.5 Incompatible materialsStrong acids/alkalis, strong oxidising/reducing agents.10.6 Hazardous decomposition productsUnder fire conditions, may decompose and emit toxic fumes.O
19、ther decomposition products - no data available.11.TOXICOLOGICAL INFORMATION11.1 Information on toxicological effectsAcute toxicityClassified based on available data. For more details, see section 2Skin corrosion/irritationClassified based on available data. For more details, see section 2Serious ey
20、e damage/irritationClassified based on available data. For more details, see section 2Respiratory or skin sensitizationClassified based on available data. For more details, see section 2Germ cell mutagenicityClassified based on available data. For more details, see section 2CarcinogenicityIARC: No c
21、omponent of this product present at a level equal to or greater than 0.1% is identified as probable, possible orconfirmed human carcinogen by IARC.ACGIH: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmedcarcinogen by ACGIH.NTP: No
22、 component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmedcarcinogen by NTP.OSHA: No component of this product present at a level equal to or greater than 0.1% is identified as a potential or confirmedcarcinogen by OSHA.Reproductive toxici
23、tyClassified based on available data. For more details, see section 2Specific target organ toxicity - single exposureClassified based on available data. For more details, see section 2Specific target organ toxicity - repeated exposureClassified based on available data. For more details, see section
24、2Aspiration hazardClassified based on available data. For more details, see section 212. ECOLOGICAL INFORMATION12.1 ToxicityNo data available.12.2 Persistence and degradabilityNo data available.12.3 Bioaccumlative potentialNo data available.12.4 Mobility in soilNo data available.Page 4 of 5 www.MedC
25、hemE12.5 Results of PBT and vPvB assessmentPBT/vPvB assessment unavailable as chemical safety assessment not required or not conducted.12.6 Other adverse effectsNo data available.13. DISPOSAL CONSIDERATIONS13.1 Waste treatment methodsProductDispose substance in accordance with prevailing country, fe
26、deral, state and local regulations.Contaminated packagingConduct recycling or disposal in accordance with prevailing country, federal, state and local regulations.14. TRANSPORT INFORMATIONDOT (US)This substance is considered to be non-hazardous for transport.IMDGThis substance is considered to be no
27、n-hazardous for transport.IATAThis substance is considered to be non-hazardous for transport.15. Inhibitors, Agonists, Screening Librarieswww.MedChemEData SheetBIOLOGICAL ACTIVITY: SAR405838 is a highly potent and selective MDM2 inhibitor, binds to MDM2 with Ki= 0.88 nM and has high specificity over
28、 otherproteins.IC50 value: 0.88 nM (Ki) 1Target: MDM2in vitro: SAR405838 potently inhibits cell growth in cancer cell lines, including SJSA1 (IC50, 0.092 M), RS4;11 (IC50, 0.089 M), LNCaP(IC50, 0.27 M), and HCT116 (IC50, 0.20 M) cells, and displays high selectivity over cancer cell lines with mutate
29、d or deleted p53,including SAOS2 (IC50, 10 M), PC3 (IC50, 10 M), SW620 (IC50, 10 M), and HCT116 (p53/) (IC50, 20 M) cells.1SAR405838 effectively induces apoptosis in the RS4;11 cell line. SAR405838 potently inhibits cell growth and induces dosedependentapoptosis in the ABTR1 and ABTR2 sublines, albe
30、it with modestly reduced potency compared with that in the control RS4;11 cellline.2in vivo: At welltolerated dose schedules, SAR405838 achieves either durable tumor regression or complete tumor growth inhibition inmouse xenograft models of SJSA1 osteosarcoma, RS4;11 acute leukemia, LNCaP prostate c
31、ancer and HCT116 colon cancer.Remarkably, a single oral dose of SAR405838 is sufficient to achieve complete tumor regression in the SJSA1 model. In the SJSA1osteosarcoma, acute lymphoblastic leukemia RS4;11, LNCaP prostate cancer, and HCT116 colon cancer xenograft model, MI773(p.o.) effectively inhi
32、bits tumor growth in a dosedependent manner (10 mg/kg, 30 mg/kg, 50 mg/kg, 100 mg/kg, and 200 mg/kg,). 1PROTOCOL (Extracted from published papers and Only for reference) Kinase assay 1 Binding affnities of MDM2 inhibitors and p53 peptide to MDM2 protein are determined using anFluorescencepolarizatio
33、n (FP) binding assay. Binding affnities of SAR405838 to Bcl2, BclxL, Mcl1, and catenin are determinedusing a competitive FPbased assay, and its binding affinity to MDMx is determined using Biolayer Interferometry technology. Cellassay 2 Cells were treated with SAR405838 for 4 days for cell viability
34、 analysis using a WST assay. Apoptosis analysis by flowcytometry with Annexin V/PI double staining. RS4;11/shControl, G3M1/shControl, and G3M1/shBAK cells were treated withSAR405838 for 24 hours. Animal administration 1 For in vivo efficacy experiments, when tumors reached 100200 mm3, mice wererando
35、mized into groups of 8 SCID mice (LNCaP in males and other three models in females), except in the HCT116 and single doseSJSA1 efficacy experiments, in which 6 mice per group were used. Vehicle Control (10% PEG400: 3% Cremophor: 87% PBS, or2%TPGS:98%PEG200), or SAR405838 was given orally once per da
36、y for the indicated dose and duration. Statistical analyses were doneby twoway ANOVA and unpaired twotailed t test, using Prism (version 4.0, GraphPad).References: 1. Wang S, et al. SAR405838: an optimized inhibitor of MDM2p53 interaction that induces complete and durable tumor regression. Cancer Re
37、s. 2014 OctProduct Name: SAR405838Cat. No.: HY-18986CAS No.: 1303607-60-4Molecular Formula:C29H34Cl2FN3O3Molecular Weight: 562.50Target: MDM2/p53Pathway: ApoptosisSolubility: 10 mM in DMSOwww.MedChemE15;74(20):58555865.2. HoffmanLuca CG, et al. Elucidation of Acquired Resistance to Bcl2 and MDM2 Inh
38、ibitors in Acute Leukemia In Vitro and In Vivo. Clin Cancer Res. 2015Jun 1;21(11):25582568.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: techMedChemEAddress: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USAwww.MedChemE
