AZD2932_DataSheet_MedChemExpress
Gelucire-14-44-SDS-MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:Nov.-23-2018Print Date:Nov.-23-20181. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :Gelucire 14/44Catalog No. :HY-Y1892CAS No. :121548-04-71.2 Relevant identified uses of the substance or 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:sales@1.4 Emergency telephone numberEmergency Phone #:609-228-68982. HAZARDS IDENTIFICATION2.1 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:NoneFormula:N/AMolecular Weight:N/ACAS No. :121548-04-74. 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 eyelids with fingers to ensure adequate flushing. Promptly 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 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 attention 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 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 ventilation. Evacuate personnel to 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 liquid-binding material (diatomite, universal binders); Decontaminate surfaces and equipment 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 and aerosol formation. Use only in areas with appropriate exhaust ventilation.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:Pure form-20°C 3 years4°C 2 yearsIn solvent-80°C 6 months-20°C 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 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 Impervious clothing.Respiratory protection Suitable respirator.Environmental exposure controls Keep 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 White to off-white (Oil)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 limits No 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 temperature 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.10.3 Possibility of hazardous reactionsNo 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.Other 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 eye 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 component of this product present at a level equal to or greater than 0.1% is identified as probable, possible or confirmed 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 confirmed carcinogen by ACGIH.NTP: No component of this product present at a level equal to or greater than 0.1% is identified as a anticipated or confirmed carcinogen 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 confirmed carcinogen by OSHA.Reproductive toxicityClassified 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 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.12.5 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, federal, 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 non-hazardous for transport.IATAThis substance is considered to be non-hazardous for transport.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 313 Components:This material does not contain any chemical components with known CAS numbers that exceed the threshold (De Minimis) reporting levels established by SARA Title III, Section 313.SARA 311/312 Hazards:No SARA Hazards.Massachusetts Right To Know Components:No components are subject to the Massachusetts Right to Know Act.Pennsylvania Right To Know Components:No components are subject to the Pennsylvania Right to Know Act.New Jersey Right To Know Components:No components are subject to the New Jersey Right to Know Act.California Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductive harm.16. OTHER INFORMATIONCopyright 2018 MedChemExpress. The above information is correct to the best of our present knowledge but does not purport to be all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It must only be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safe use of this material rests entirely with the user. MedChemExpress disclaims all liability for any damage resulting from handling or from contact with this product.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
AZD-9291_mesylate_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:AZD–9291 mesylate is a third generation irreversible EGFR tyrosine kinase inhibitor with selectivity against mutant versus wild–type forms of EGFR , shows an apparent IC 50 of 12 nM against L858R and 1 nM against L858R/T790M in EGFR recombinant enzyme assay.IC50 & Target: IC50: 1 nM (EGFR L858R/T790M ), 12 nM (EGFR L858R )[1]In Vitro: AZD–9291 (AZD9291) shows similar potency to early generation tyrosine kinase inhibitor (TKIs) in inhibiting EGFRphosphorylation in EGFR cells harboring sensitising EGFR mutants including PC–9 (ex19del), H3255 (L858R) and H1650 (ex19del),with mean IC 50 values ranging from 13 to 54 nM for AZD–9291. AZD–9291 also potently inhibits phosphorylation of EGFR in T790M mutant cell lines (H1975 (L858R/T790M), PC–9VanR (ex19del/T790M), with mean IC 50 potency less than 15 nM [1].In Vivo: The tumor–bearing mice are treated with AZD–9291 (5 mg/kg/day) for one to two weeks. Within days of treatment, 5 of 5C/L858R mice displays nearly 80% reduction in tumor volume by magnetic resonance imaging MRI after therapy with AZD–9291,while 5 of 5 mice treated with vehicle shows tumor growth [1]. AZD–9291 demonstrates improved rat PK, reduced hERG affinity, and improved IGF1R margins relative to the previously described compounds, and so this compound is selected for furtherinvestigation. AZD–9291 also offers an additional degree of broader chemical and profile diversity when compared to thepreviously described lead compounds. Upon dosing AZD–9291 in three efficacy models, The comparable efficacy is observed at relatively low doses (10 mg/kg per day). The excellent efficacy is also observed when AZD–9291 is dosed at 5 mg/kg per day [2].PROTOCOL (Extracted from published papers and Only for reference)Cell Assay: AZD–9291 is dissolved in DMSO and stored, and then diluted with appropriate medium before use [1]. [1]PC–9 cells are seeded into T75 flasks (5×105 cells/flask) in RPMI growth media and incubated at 37°C, 5% CO 2. The following day the media is replaced with media supplemented with a concentration of EGFR inhibitor equal to the EC 50 concentration predetermined in PC–9cells. Media changes are carried out every 2–3 days and resistant clones allowed to grow to 80% confluency prior to the cells being trypsinised and reseeded at the original seeding density in media containing twice the concentration of EGFR inhibitor. Doseescalations are continued until a final concentration of 1.5 μM Gefitinib, 1.5 μM Afatinib, 1.5 μM WZ4002 or 160 nM AZD–9291 are achieved [1].Animal Administration: AZD–9291 is suspended in 1% Polysorbate 80 (Mice)[1].AZD–9291 is suspended in 0.5% w/v HPMC/0.1% w/v Tween in deionized water at a concentration of 20 mg/mL (Rat)[2]. [1][2]Mice [1]The EGFR L858R and EGFR L858R+T790M mice (male and female) are used. AZD–9291 is suspended in 1% Polysorbate 80 and administered via oral gavage once daily at the doses of 7.5 mg/kg and 5 mg/kg, respectively. Mice are imaged weekly at theVanderbilt University Institute of Imaging Science. For immunoblot analysis, mice are treated for eight hours with drug as described before dissection and flash freezing of the lungs. Lungs are pulverized in liquid nitrogen before lysis.Rat [2]Product Name:AZD–9291 (mesylate)Cat. No.:HY-15772A CAS No.:1421373-66-1Molecular Formula:C 29H 37N 7O 5S Molecular Weight:595.71Target:EGFR; EGFR Pathway:JAK/STAT Signaling; Protein Tyrosine Kinase/RTK Solubility:DMSOThe male RccHan:WIST rats (10–week–old) are received a single oral dose of AZD–9291 (200 mg/kg). Blood glucose levels are measured using an Accuchek Active meter. Serum insulin concentrations are determined using a commercial rat ELISA kit.References:[1]. Cross DA, et al. AZD9291, an irreversible EGFR TKI, overcomes T790M–mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014 Sep; 4(9):1046–61.[2]. Finlay MR, et al. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistancemutations that spares the wild type form of the receptor. J Med Chem. 2014 Oct 23;57(20):8249–67.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
AZD1981_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:AZD1981 is a potent and selective CRTh2 antagonist; displaces radio–labelled PGD2 from human recombinant DP2 with high potency (pIC50 = 8.4).IC50 value:Target: GPR44 antagonistin vitro: AZD1981 produced a concentration–dependent displacement of the [3H]PGD2–specific binding with a mean pIC50 of 8.4 ±0.1 (n = 25, geometric mean IC50 of 4 nM). AZD1981 had no significant affinity towards recombinant human DP1 receptors with only a mean 27% (range 14–50%; n = 4) displacement of [3H]PGD2–specific binding observed at the highest concentration tested (10 μM).Compared with the binding potency for DP2, AZD1981 showed 10–fold selectivity over rat aldose reductase and 1700–fold selectivity over rat steroid 5α–reductase.In eosinophils, a single concentration of 1 μM, AZD1981 caused a large (20–fold) rightward parallel shift in the 15R–methyl PGD2 E/[A] curve with no evidence of a decrease in the maximal response. The effect of AZD1981 was therefore investigated using a single sub–maximal concentration of agonist (1 μM). AZD1981 produced a concentration–dependent inhibition of eosinophil migration with a pIC50 value of 7.6 ± 0.1 (n = 4) [1].in vivo: Using the previously described guinea pig hind limb model , 10 nM AZD1981 significantly inhibited DK–PGD2–induced eosinophil mobilization by approximately 50%, and the response was completely inhibited with 100 nM AZD1981 [1].in vivo: AZD1981 exhibited good cross–species binding activity against mouse, rat, guinea pig, rabbit and dog DP2 . Evaluation inmouse, rat or rabbit cell systems was not possible as they did not respond to DP2 agonists. Agonist responses were seen in guinea pig and dog, and AZD1981 blocked DP2 –mediated eosinophil shape change. Such responses were more robust in the guinea pig, where AZD1981 also blocked DP2 –dependent eosinophil emigration from bone marrow [1]. There was no beneficial clinical effect ofAZD1981, at a dose of 1000 mg twice daily for 4 weeks, in patients with moderate to severe COPD. AZD1981 was well tolerated and no safety concerns were identified [3].PROTOCOL (Extracted from published papers and Only for reference)Cell assay [1]Assays contained AZD1981 or vehicle control [2 μL at 50 times the required final concentration in HBSS/HEPES containing 5%dimethyl sulphoxide (DMSO)], 78 μL of cell suspension, 10 μL of antibody mix or isotype control and 10 μL of agonist[13,14–dihydro–15–keto–PGD2. AZD1981 was pre–incubated with cells for 15 min before addition of the antibody mix and agonist.After incubation for 15 min at 37°C, cells were fixed by addition of 10 μL of ice–cold autologous plasma followed by 100 μL of ice–cold 0.05% formaldehyde in HBSS/HEPES and left in the dark for 15 min at room temperature. Fixed cells were transferred to tubes suitable for use with the flow cytometer, red blood cell lysis solution (150 mM NH4Cl, 10 mM KHCO3 1.27 mM EDTA pH 7.0, 800 μL) added,and the cells were incubated at room temperature for 10 min. Cells were finally pelleted by centrifugation (530× g for 5 min room temperature) and re–suspended in 0.3 mL of PBS containing 0.1% v/v CellFIX? (Beckton Dickinson, Cowley, UK). CD11b expression wasProduct Name:AZD1981Cat. No.:HY-15950CAS No.:802904-66-1Molecular Formula:C 19H 17ClN 2O 3S Molecular Weight:388.87Target:CRTH2 (GPR44); CRTH2 (GPR44)Pathway:GPCR/G Protein; Immunology/Inflammation Solubility:DMSO: ≥ 31 mg/mLdetermined by flow cytometry. The eosinophil population within the granulocytes was gated on the basis of forward scatter/side scatter profile and low CD16 expression. CD11b expression was measured as the median peak fluorescence (MdX value) through FL–1. Animal administration:Please refer to /pubmed/18837743/.References:[1]. Royer JF, et al. A novel antagonist of prostaglandin D2 blocks the locomotion of eosinophils and basophils. Eur J Clin Invest. 2008 Sep;38(9):663–71.[2]. Luker T, et al. Substituted indole–1–acetic acids as potent and selective CRTh2 antagonists–discovery of AZD1981. Bioorg Med Chem Lett. 2011 Nov 1; 21(21):6288–92.[3]. Snell N, et al. Efficacy and safety of AZD1981, a CRTH2 receptor antagonist, in patients with moderate to severe COPD. Respir Med. 2013 Nov;107(11):1722–30.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
埃博霉素类似物、其制备方法、药物组合物及用途[发明专利]
![埃博霉素类似物、其制备方法、药物组合物及用途[发明专利]](https://img.taocdn.com/s3/m/0944c8eb844769eae109ed7a.png)
专利名称：埃博霉素类似物、其制备方法、药物组合物及用途专利类型：发明专利
发明人：张晓东,谢国建,郇正伟,查理斯·大卫,王印祥,陈杭
申请号：CN200410066561.8
申请日：20040922
公开号：CN1752078A
公开日：
20060329
专利内容由知识产权出版社提供
摘要：本发明涉及埃博霉素类似物、其制备方法、含有该类似物的药物组合物以及该类似物的使用方法。
本发明埃博霉素类似物可用于治疗各种癌症或其它各种增生性疾病，包括与微管稳定化相关的各种疾病。
本发明化合物还可以用于诱导细胞程序死亡。
申请人：贝达医药开发(上海)有限公司
地址：200336 上海市遵义南路8号锦明大厦12A
国籍：CN
代理机构：上海专利商标事务所有限公司
代理人：徐迅
更多信息请下载全文后查看。
安捷伦产品目录
15
Real-Time PCR
16
Mx3000P QPCR System
17
Brilliant III Ultra-Fast SYBR Green QPCR and QRT-PCR Reagents
18
Brilliant III Ultra-Fast QPCR and QRT-PCR Reagents
Agilent / STRATAGENE
Agilent website: /genomics
Welgene | Agilent Stratagene
威健股份有限公司 | Stratagene 總代理
Table of Content
Table of Contents
/ XL1-Red Competent Cells SoloPack Gold Supercompetent Cells
/ TK Competent Cells Specialty Cells
/ Classic Cells / Fine Chemicals For Competent Cells
適用於 UNG 去汙染或 bisulphite
sequencing
適用於 TA Cloning
最高敏感性
取代傳統 Taq 的好選擇
-
2
威健股份有限公司 | Stratagene 總代理
PCR Enzyme & Instrument
Agilent SureCycler 8800
市場上領先的 cycling 速度和 sample 體積 10 ～ 100 μL 簡易快速可以選擇 96 well 和 384 well 操作盤 優秀的溫控設備讓各個 well 都能保持溫度的穩定 七吋的高解析度觸控螢幕讓操作上更為簡便 可以透過網路遠端操控儀器及監控儀器 Agilent 專業的技術支援可以幫助您應對各種 PCR 的問題
CHIR-99021_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:CHIR–99021 is a GSK–3α/β inhibitor with IC 50 of 10 nM/6.7 nM; > 500–fold selectivity for GSK–3 versus its closest homologs CDC2 and ERK2, as well as other protein kinases.IC50 & Target: IC50: 10 nM/6.7 nM (GSK–3α/β)[1]In Vitro: CHIR 99021inhibits human GSK–3β with K i values of 9.8 nM [1]. CHIR 99021 is a small organic molecule that inhibits GSK3α and GSK3β by competing for their ATP–binding sites.In vitro kinase assays reveal that CHIR 99021 specifically inhibits GSK3β (IC 50=~5 nM) and GSK3α (IC 50=~10 nM), with little effect on other kinases [2]. In the presence of CHIR–99021 the viability of the ES–D3 cells is reduced by 24.7% at 2.5 μM, 56.3% at 5 μM, 61.9% at 7.5 μM and 69.2% at 10 μM CHIR–99021 with an IC 50 of 4.9μM [3].In Vivo: In ZDF rats, a single oral dose of CHIR 99021 (16 mg/kg or 48 mg/kg) rapidly lowers plasma glucose, with a maximal reduction of nearly 150 mg/dl 3–4 h after administration [1]. CHIR99021 (2 mg/kg) given once, 4 h before irradiation, significantly improves survival after 14.5 Gy abdominal irradiation (ABI). CHIR99021 treatment significantly blocks crypt apoptosis andaccumulation of p–H2AX + cells, and improves crypt regeneration and villus height. CHIR99021 treatment increases Lgr5+ cellsurvival by blocking apoptosis, and effectively prevents the reduction of Olfm4, Lgr5 and CD44 as early as 4 h [4].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[2]Kinases are purified from SF9 cells through use of their His or Glu tag. Glu–tagged proteins are purified, and His–tagged proteins are purified. Kinase assays are performed in 96–well plates with appropriate peptide substrates in a 300–μL reaction buffer (variations on 50 mM Tris–HCl, pH 7.5, 10 mM MgCl 2, 1 mM EGTA, 1 mMdithiothreitol, 25 mMβ–glycerophosphate, 1mM NaF, and 0.01% bovine serum albumin). Peptides has K m values from 1 to 100 μM. CHIR 99021 or CHIR GSKIA is added in 3.5μL of Me 2SO, followed by ATP to a final concentration of 1 μM. After incubation, triplicate 100–μL aliquots are transferred to Combiplate 8 plates containing 100 μL/well of 50 μM ATP and 20 mM EDTA. After 1 hour, the wells are rinsed five times with phosphate–buffered saline, filled with 200 μL of scintillation fluid, sealed, and counted in a scintillation counter 30 min later. All of the steps are at room temperature. The percentage of inhibition is calculated as 100×(inhibitor–no enzyme control)/(Me 2SO control–no enzyme control)[2].Cell Assay: CHIR 99021 is dissolved in DMSO and stored, and then diluted with appropriate media before use [3].[3]The viability of the mouse ES cells is determined after exposure to different concentrations of GSK3 inhibitors for three days using the MTT assay.The decrease of MTT activity is a reliable metabolism–based test for quantifying cell viability; this decrease correlates with the loss of cell viability. 2,000 cells are seeded overnight on gelatine–coated 96–well plates in LIF–containing ES cell medium. On the next day the medium is changed to medium devoid of LIF and with reduced serum and supplemented with 0.1–1 μM BIO, or 1–10 μM SB–216763, CHIR–99021 or CHIR–98014. Basal medium without GSK3 inhibitors or DMSO is used as control. All tested conditions are analyzed in triplicates [3].Product Name:CHIR–99021Cat. No.:HY-10182CAS No.:252917-06-9Molecular Formula:C 22H 18Cl 2N 8Molecular Weight:465.34Target:GSK–3; GSK–3; Autophagy Pathway:Stem Cell/Wnt; PI3K/Akt/mTOR; Autophagy Solubility:DMSO: ≥ 5.1 mg/mLAnimal Administration: CHIR 99021 is formulated as solutions in 20 mM citrate–buffered 15% Captisol or as fine suspensions in0.5% carboxymethylcellulose (Rat)[1].CHIR 99021 is prepared in DMSO and diluted (Mice)[4].[1][4]Rat[1]Primary hepatocytes from male Sprague Dawley rats that weighed <140 g are prepared and used 1–3 h after isolation. Aliquotsof 1×106cells in 1 mL of DMEM/F12 medium plus 0.2% BSA and CHIR 99021(orally at 16 or 48 mg/kg) or controls are incubated in 12–well plates on a low–speed shaker for 30 min at 37°C in a CO2–enriched atmosphere, collected by centrifugation and lysed by freeze/thaw in buffer A plus 0.01% NP40; the GS assay is again performed.Mice[4]Mice 6–10 weeks old are used. The PUMA+/+ and PUMA–/– littermates on C57BL/6 background (F10) and Lgr5–EGFP(Lgr5–EGFP–IRES–creERT2) mice are subjected to whole body irradiation (TBI), or abdominal irradiation (ABI). Mice are injected intraperitoneally (i.p.) with 2 mg/kg of CHIR99021 4 h before radiation or 1 mg/kg of SB415286 28 h and 4 h before radiation. Mice are sacrificed to collect small intestines for histology analysis and western blotting. All mice are injected i.p. with 100 mg/kg of BrdU before sacrifice.References:[1]. Ring DB, et al. Selective glycogen synthase kinase 3 inhibitors potentiate insulin activation of glucose transport and utilization in vitro and in vivo. Diabetes. 2003 Mar;52(3):588–95.[2]. Bennett CN, et al. Regulation of Wnt signaling during adipogenesis. J Biol Chem. 2002 Aug 23;277(34):30998–1004.[3]. Naujok O, et al. Cytotoxicity and activation of the Wnt/beta–catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors.BMC Res Notes. 2014 Apr 29;7:273.[4]. Wang X, et al. Pharmacologically blocking p53–dependent apoptosis protects intestinal stem cells and mice from radiation. Sci Rep. 2015 Apr 10;5:8566.Caution: Product has not been fully validated for medical applications. For research use only.Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。
GSK2879552_LCMS_19698_MedChemExpress
=====================================================================Acq. Operator : admin Seq. Line : 16Acq. Instrument : HY-LCMS-02 Location : P2-F-07Injection Date : 3/4/2016 10:51:38 AM Inj : 1Inj Volume : 3.000 µlAcq. Method : D:\AGLIENT 1260\DATA\20160304\20160304 2016-03-04 09-41-28\100-1000MS+3MIN- 1.5_(0.02%FA).MLast changed : 3/4/2016 9:41:29 AM by adminAnalysis Method : D:\AGLIENT 1260\DATA\20160304\20160304 2016-03-04 09-41-28\100-1000MS+3MIN- 1.5_(0.02%FA).M (Sequence Method)Last changed : 3/4/2016 11:30:25 AM by Su Xiao Ying(LCMS-02) (modified after loading)Method Info : Postive,MS:100-1000,Column ID:A-RP-132,40℃Catalog No : HY-18632 Batch#19698 A-RP-134Additional Info : Peak(s) manually integratedmin0.511.522.53mAU 0100200300400500600700 DAD1 B, Sig=214,4 Ref=off (D:\AGLIENT 1260\DATA\20160304\20160304 2016-03-04 09-41-28\BIZ2016-304-WJ4.D)1.3322.7663.022===================================================================== Area Percent Report =====================================================================Sorted By : Signal Multiplier : 1.0000Dilution : 1.0000Do not use Multiplier & Dilution Factor with ISTDsSignal 1: DAD1 B, Sig=214,4 Ref=offPeak RetTime Type Width Area Height Area # [min] [min] [mAU*s] [mAU] %----|-------|----|-------|----------|----------|--------| 1 1.332 MM 0.0690 3231.35596 780.95398 99.8220 2 2.766 MM 0.0469 2.66797 9.47122e-1 0.0824 3 3.022 MM 0.0462 3.09431 1.11593 0.0956Totals : 3237.11824 783.01703===================================================================== *** End of Report ***=====================================================================Acq. Operator : admin Seq. Line : 16Acq. Instrument : HY-LCMS-02 Location : P2-F-07Injection Date : 3/4/2016 10:51:38 AM Inj : 1Inj Volume : 3.000 µlAcq. Method : D:\AGLIENT 1260\DATA\20160304\20160304 2016-03-04 09-41-28\100-1000MS+3MIN- 1.5_(0.02%FA).MLast changed : 3/4/2016 9:41:29 AM by adminAnalysis Method : D:\AGLIENT 1260\DATA\20160304\20160304 2016-03-04 09-41-28\100-1000MS+3MIN- 1.5_(0.02%FA).M (Sequence Method)Last changed : 3/4/2016 11:28:29 AM by Su Xiao Ying(LCMS-02) (modified after loading)Method Info : Postive,MS:100-1000,Column ID:A-RP-132,40℃Catalog No : HY-18632 Batch#19698 A-RP-134Additional Info : Peak(s) manually integratedmin0.511.522.53100000200000300000400000500000600000700000800000 MSD1 TIC, MS File (D:\AGLIENT 1260\DATA\20160304\20160304 2016-03-04 09-41-28\BIZ2016-304-WJ4.D) ES-API, Pos, Scan1.341MS Signal: MSD1 TIC, MS File, ES-API, Pos, Scan, Frag: 50 Spectra averaged over upper half of peaks. Noise Cutoff: 1000 counts.Reportable Ion Abundance: > 10%.Retention Mol. Weight Time (MS) MS Area or Ion1.341 5571005 366.30 I 365.30 I 249.20 I 183.20 I 117.20 Im/z10020030040050060070020406080100*MSD1 SPC, time=1.307:1.380 of D:\AGLIENT 1260\DATA\20160304\20160304 2016-03-04 09-41-28\BIZ2016-304-WJ4.D ES-API, Max: 382899366.3117.2249.2365.3183.2*** End of Report ***。
高效液相色谱-串联质谱法同时测定3种N-亚硝胺类基因毒性杂质
高效液相色谱-串联质谱法同时测定3种N-亚硝胺类基因毒性杂质徐艳梅;韩彬;郝丽娟;高燕霞【期刊名称】《医药导报》【年(卷),期】2022(41)11【摘要】目的建立高效液相色谱-串联质谱(HPLC-MS/MS)法同时测定厄贝沙坦原料药中3种N-亚硝胺类基因毒性杂质(N-亚硝基乙基异丙胺、N-亚硝基二异丙胺和N-亚硝基二丁胺)。
方法采用Agilent 120 PFP色谱柱(100 mm×2.1mm,2.7μm),流动相为甲醇(A)-0.1%甲酸(B),梯度洗脱,流速0.4 mL·min^(-1),柱温40℃;采集模式为正离子,监测模式为质谱多反应监测。
结果N-亚硝基乙基异丙胺、N-亚硝基二异丙胺和N-亚硝基二丁胺在各自线性范围内线性关系良好(R^(2)≥0.9997),平均加样回收率分别为95.13%,92.00%和93.96%,RSD分别为4.22%,3.25%和3.60%。
结论该方法简单、快速,灵敏度高,准确性强,重复性好,可用于厄贝沙坦原料药中N-亚硝胺类基因毒性杂质的检测。
【总页数】5页(P1672-1676)【作者】徐艳梅;韩彬;郝丽娟;高燕霞【作者单位】河北省药品医疗器械检验研究院【正文语种】中文【中图分类】R972;R927.1【相关文献】1.高效液相色谱－串联质谱法测定主流烟气总粒相物中烟草特有N－亚硝胺的不确定度评定2.固相萃取净化及超高效液相色谱-串联质谱法测定橡胶制品中的13种N-亚硝胺3.超高效液相色谱-串联质谱法快速测定苯磺酸酯类基因毒性杂质4.超高效液相色谱-串联质谱法测定叔胺类药品中硫酸二甲酯基因毒性杂质5.高效液相色谱串联质谱法检测阿奇霉素原料药及其制剂中6种N-亚硝胺类基因毒性杂质因版权原因，仅展示原文概要，查看原文内容请购买。
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
Inhibitors, Agonists, Screening Libraries
Data Sheet
BIOLOGICAL ACTIVITY:
AZD2932 is a new series of quinazoline ether inhibitor which potently inhibits VEGFR–2 and PDGFR with IC50s of 4 nM/8 nM/ 7 nM for PDGFRβ/VEGFR–2/Flt–3.
IC50 value: 4/8/7 nM(PDGFRβ/VEGFR–2/Flt–3) [1]
Target: PDGFRβ/VEGFR2
The same C6 in vivo model was used to study tumor growth inhibition (TGI) with AZD2932. Twice daily oral dosing (b.i.d.) 10 h apart resulted in significant TGI of 64% for both 50 and 12.5 mg/kg doses on the day the control animals were terminated (day 22 on the graph). Most importantly, xenografts bearing non–PDGFR expressing tumor cells were also sensitive to AZD2932 treatment: growth of Calu–6 tumor was inhibited by 81% and 72% at 50 and 12.5 mg/kg b.i.d. (p <0.001) and LoVo tumors by 67% at 50 mg/kg b.i.d. (p <0.001)[1].
PROTOCOL (Extracted from published papers and Only for reference)
Animal administration [1]
The female nude mice bearing C6 tumors from the above experiment are dosed iv with VEGF–A and PDGFBB 5 min prior to cull and 6h post last dose ofAZD2932 and the lungs excised immediately after. Lung lysates are analyzed by western blot for total and phosphorylated VEGFR–2 and PDGFRβ. AZD2932 at 3–50 mg/kg b.i.d. 10 h apart gave 60–80% inhibition of both p–VEGFR–2 and p–PDGFRβ in a 1:1 ratio.
References:
[1]. Plé PA, et al. Discovery of AZD2932, a new Quinazoline Ether Inhibitor with high affinity for VEGFR–2 and PDGFR tyrosine kinases. Bioorg Med Chem Lett.2012 Jan 1;22(1):262–6.
Product Name:
AZD2932Cat. No.:
HY-18179CAS No.:
883986-34-3Molecular Formula:
C 24H 25N 5O 4Molecular Weight:
447.49Target:
PDGFR; VEGFR Pathway:
Protein Tyrosine Kinase/RTK; Protein Tyrosine Kinase/RTK Solubility:
DMSO: ≥ 41 mg/mL
Caution: Product has not been fully validated for medical applications. For research use only.
Tel: 609-228-6898 Fax: 609-228-5909 E-mail: tech@ Address: 1 Deer Park Dr, Suite Q, Monmouth Junction, NJ 08852, USA。