1、 Inhibitors, Agonists, Screening Librarieswww.MedChemEData SheetBIOLOGICAL ACTIVITY: PD173955 is src familyselective tyrosine kinase inhibitor with IC50 of 22 nM for Src, Yes and Abl kinase; less potent for FGFR andno activity on InsR and PKC.IC50 value: 22 nMTarget: Src kinase inhibitorin vitro: PD
2、173955 inhibits the growth of MDAMB468 and MCF7 breast cancer cells with IC50s of 500 nM and 1 M, respectively,with an accumulation of suspended cells. Cells treated with PD173955 show a near complete redistribution to the G2M phase of thecell cycle in comparison with control cells, and quantitation
3、 of mitotic indices by immunofluorescence microscopy shows anaccompanying accumulation of mitotic cells.PD173955 shows antimitotic activity in breast cancer cells with high or low src and yeskinase activities, the antimitotic activity of PD173955 is independent of cell type or malignant transformati
4、on 1. PD173955 inhibitsboth the active and inactive forms of Abl. By contrast, Imatinib only inhibits the active form of the enzyme. In addition, the Ki forinhibition of Abl by PD173955 is very low, making it a more potent inhibitor of Abl and a more effective inhibitor of cancer cellproliferation t
5、han Imatinib 2. PD173955, a Src familyspecific tyrosine kinase inhibitor, increases the susceptibility of HT29 cells toanoikis in a dose and timedependent manner 3.PROTOCOL (Extracted from published papers and Only for reference) Kinase Assay(Src kinase) 1: For src kinase assays, total cellular lysa
6、tes were harvested in modified RIPA buffer 1% sodiumdeoxycholate, 1% NP40, 0.1% SDS, 150 mM NaCl, and 10 mM sodium phosphate (pH 7.2) supplemented with 10 M aprotinin, 10 Mleupeptin, 1 mM sodium orthovanadate, and 1 mM phenylmethylsulfonyl fluoride. Total cellular lysates (300 g) were incubated with
7、antibodies specific for each of the src family kinases and immunoprecipitated using protein GSepharose (Pharmacia).Immunoprecipitates were washed twice in cold lysis buffer and once in kinase buffer and added to an in vitro kinase reactionconsisting of 50 mM PIPES (pH 7.0), 10 mM MnCl2, 10 mM DTT, 1
8、0 M ATP, 2 g of aciddenatured enolase, and 5 Ci of 32PATP.Reactions were allowed to proceed at 30C for 5 min and then stopped immediately by boiling in sample buffer, products separatedon a 10% SDSPAGE gel, transferred to membrane, and exposed to film. Monoclonal antibodies specific for src (m327; C
9、albiochem),cyes (1B7; Wako), lyn (LO5620; Transduction Laboratories), and polyclonal antifyn antibodies (SC16; Santa Cruz Biotechnology)were used in immunoprecipitations and in immunoblotting, using the appropriate secondary immunological reagents. Cell Cycle Assay1: All cell lines were obtained fro
10、m the American Type Culture Collection; maintained in a 1:1 mixture of DMEM:Hams F12supplemented with 100 units/ml penicillin, 100 g/ml streptomycin, 4 mM glutamine, and 10% heatinactivated fetal bovine serum;and incubated at 37C in 5% CO2. PD173955 was maintained as a 10 mM frozen stock solution in
11、 DMSO. For determination of cellcycle effects, cells were seeded at approximately 2 million cells/10cm dish and placed the next day in media containing 5 MPD173955 or an equal volume of DMSO. After 24 or 48 h, cells were harvested by trypsinization, taking care to preserve all suspendedand adherent
12、cell populations. After washing in cold PBS, cell nuclei were prepared by the method of Nusse et al. and cell cycleProduct Name: PD173955Cat. No.: HY-10395CAS No.: 260415-63-2Molecular Formula:C21H16Cl2N4OSMolecular Weight: 443.35Target: BcrAbl; SrcPathway: Protein Tyrosine Kinase/RTKSolubility: DMS
13、O: 32 mg/mLwww.MedChemEdistribution was determined by flow cytometric analysis of DNA content using red fluorescence of 488 nm excited ethidiumbromidestained nuclei. For determination of mitotic indices, aliquots of cells were fixed in 3% paraformaldehyde, stained in 24 g/mlbisbenzimide, and analyze
14、d under fluorescence microscopy. Mitotic cells were identified by their characteristic chromatincondensation. A total of 1000 cells were counted, and the percentage of cells in mitosis was calculated.References: 1. Moasser MM, et al. Inhibition of Src kinases by a selective tyrosine kinase inhibitor
15、 causes mitotic arrest. Cancer Res. 1999 Dec 15;59(24):614552.2. Kraus GA, et al. New effective inhibitors of the Abelson kinase. Bioorg Med Chem. 2010 Sep 1;18(17):631621.3. Windham TC, et al. Src activation regulates anoikis in human colon tumor cell lines. Oncogene. 2002 Nov 7;21(51):7797807.Caut
16、ion: 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撠撠ORMATIONSARA 302 Components:No chemicals in this material are subject to t
17、he 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.Massachuse
18、tts 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.Califo
19、rnia Prop. 65 Components:This product does not contain any chemicals known to State of California to cause cancer, birth defects, or anyother reproductiveharm.16. OTHER INFORMATIONCopyright 2017 MedChemExpress. The above information is correct to the best of our present knowledge but does not purpor
20、t tobe all inclusive and should be used only as a guide. The product is for research use only and for experienced personnel. It mustonly be handled by suitably qualified experienced scientists in appropriately equipped and authorized facilities. The burden of safeuse of this material rests entirely
21、with the user. MedChemExpress disclaims all liability for any damage resulting from handling orfrom 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: techMedChemEAddress: 1 Deer Park Dr,
22、 Suite Q, Monmouth Junction, NJ 08852, USAPage 5 of 5 www.MedChemE富富。行业结构：主要是指外部各种环境的变化对企业所在行业可能产生的影响，包括行业竞争的变化、产品需求的变化、细分市场的变化、营销模型的变化等。企业行为：主要是指企业针对外部的冲击和行业结构的变化，有可能采取的应对措施，包括企业方面对相关业务单元的整合、业务的扩张与收缩、营运方式的转变、管理的变革等一系列变动。经营绩效：主要是指在外部环境发生变化的情况下，企业在经营利润、产品成本、市场份额等方面的变化趋势。 19 / 17 访问网址: /非企业能力的衡量指标。5、S
23、CP产业分析模型SCP（structure-conduct-performance，结构行为绩效）模型是由美国哈佛大学产业经济学权威贝恩（Bain）、谢勒（Scherer）等人建立的。该模型提供了一个既能深入具体环节，又有系统逻辑体系的产业分析框架，即：行业结构（Structure）企业行为（Conduct）经营绩效（Performance）。SCP框架的基本涵义是，行业结构决定企业在市场中的行为，而企业行为又决定市场运行在各个方面的经济绩效。SCP模型，主要用于分析行业或者企业在受到外部冲击（主要是指行业或企业外部经济环境、政治、技术、文化变迁、消费习惯等因素的变化）时，可能的战略调整及行为
24、变化。行业结构：主要是指外部各种环境的变化对企业所在行业可能产生的影响，包括行业竞争的变化、产品需求的变化、细分市场的变化、营销模型的变化等。企业行为：主要是指企业针对外部的冲击和行业结构的变化，有可能采取的应对措施，包括企业方面对相关业务单元的整合、业务的扩张与收缩、营运方式的转变、管理的变革等一系列变动。经营绩效：主要是指在外部环境发生变化的情况下，企业在经营利润、产品成本、市场份额等方面的变化趋势。 19 / 17 访问网址: / 19 / 17 访问网址: /patients survival 28. Therapeutic angiogenesis is a potential ap
25、p- roach to stimulate neovascularization in ex- treme damaged tissue to improve limb perfu-sion and tissue regeneration 29. However, AGEs produced by long-term hyperglycemia is identified as a main r Inhibitors, Agonists, Screening Librarieswww.MedChemESafety Data SheetRevision Date:Nov.-02-2017Prin
26、t Date: Nov.-02-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name : PD173955Catalog No. : HY-10395CAS No. : 260415-63-21.2 Relevant identified uses of the substance or mixture and uses advised againstIdentified uses : Laboratory chemicals, manufacture of substances.1.3 Deta
27、ils 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 mixtureGHS Classification in accordance with 29 CFR 1910 (OSHA
28、 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 swallowed.H410 Very toxic to aquatic life with long la
29、sting 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 you feel unwell.P330 Rinse mouth.P391 Collect spillage
30、.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: PD173955Formula: C21H16Cl2N4OSMolecular Weight: 443.35CAS No. : 260415-63-24. FIRST AID MEASURES4.1 Description of f
31、irst 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 with large amounts of water. Remove contaminat
32、ed 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
个人主页
