TAPI-1_DataSheet_MedChemExpress
XMD8-87_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:XMD8–87 is a potent TNK2 inhibitor with IC 50 values of 38 and 113 nM for the D163E and R806Q mutations, respectively.IC50 & Target: IC50: 38 nM (TNK2, D163E mutation), 113 nM (TNK2, R806Q mutation)[1]In Vitro: XMD8–87 potently inhibits the growth of the TNK2 mutant expressing cell lines while having little or no effect on the control cells out to the highest tested concentrations (1,000 nM). XMD8–87 has IC 50s of 38 nM and 113 nM for the D163E and R806Q mutations. The effects of XMD8–87 on TNK2 cell lines are largely due to on–target effects on TNK2. Auto–phosphorylation of overexpressed TNK2 mutants could be blocked with TNK2 inhibitor XMD8–87[1].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[1]Kinase targets are tested with biochemical enzymatic kinase assays using the SelectScreen Kinase Profiling Service to determine IC 50 values. The compounds (XMD8–87) are assayed at 10 concentrations (3–fold serial dilutions starting from 1 μM) at an ATP concentration equal to the ATP Km [1].Cell Assay:[1]Cells are treated with the following inhibitors for 72 hours: dasatinib, AIM–100, XMD8–87 and XMD16–5. Cell viability is measured using a methanethiosulfonate (MTS)–based assay and absorbance (490 nm) is read at 1 and 3 hours after adding reagent [1].References:[1]. Maxson JE, et al. Identification and Characterization of Tyrosine Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase Inhibitor Screening and Genomic Analysis.Product Name:XMD8–87Cat. No.:HY-15811CAS No.:1234480-46-6Molecular Formula:C 24H 27N 7O 2Molecular Weight:445.52Target:Tyrosinase Pathway:Metabolic Enzyme/Protease Solubility:DMSO: ≥ 26 mg/mLCaution: 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。
PRIMA-1_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:PRIMA–1 is a mutant p53 reactivator, restores the sensitivity of TP53 mutant–type thyroid cancer cells to the histone methylation inhibitor 3–Deazaneplanocin A.IC50 & Target: p53[1]In Vitro: The cell lines are cultured in the presence of PRIMA–1 at 0–140 μM. The IC 50s are 35, 40, 50, 50, 60, 70 and 75 μM for PANC–1, HEC–1–B, SUM149, AN 3CA, Ishikawa, Panc02 and MDA–MB–231 cells, respectively [2].In Vivo: PRIMA–1 (Prima–1) is a p53–modulating agent. 150 or 300 ppm PRIMA–1 significantly suppresses (P<0.0001) lung adenocarcinoma formation by 56% and 62%, respectively, after 17 weeks and 39% and 56%, respectively, after 34 weeks.Administration of 150 or 300 ppm PRIMA–1 significantly suppresses NNK–induced total lung adenocarcinoma formation by 57% or 62% (P<0.0001), respectively, after 17 weeks of exposure and by 39% or 56% (P<0.0001), respectively, after 34 weeks of exposure.As with administration of the lower (50 ppm) dose of CP–31398, administration of the lower (150 ppm) dose of PRIMA–1also slightly increases the number of NNK–induced lung adenomas [3].PROTOCOL (Extracted from published papers and Only for reference)Cell Assay: PRIMA–1 is dissolved with DMSO and diluted with appropriate media [2].[2]A cell viability assay using yellow tetrazolium salt3–(4,5–Dimethylthiazol–2–yl)–2,5–diphenyl–tetrazolium bromide or MTT is utilized to assess the effects of the p53 SMWC on growth of human carcinoma cell lines. Cells are plated in triplicate in 96–well plates at a density of 2.5×103 cells/well in 100 μL ofcomplete medium. After 24hr incubation in a humidified 5% atmosphere at 37°C, the cells are treated with increasingconcentrations of SMWC for an additional 24 hr period and analyzed for cell growth using the MTT assay. Stock solutions (10 mM)of CP–31398 and PRIMA–1 in PBS are diluted in PBS immediately prior to use. The assay is performed as follows: a 12 mM MTT stock solution is prepared by adding 1 mL of sterile PBS to 5 mg MTT and mixing by vortex or sonication until dissolved. Once prepared, the MTT solution is stored for four weeks at 4°C protected from light.A 500 mL SDS–HCl solution consisting of 0.01 M HCl, 10% propanol and 5 gm SDS is prepared by mixing the solution gently by inversion until the SDS dissolved.100 μL of cell culture medium is removed from each well and 10 μL of the 12 mM MTT stock solution added. A negative control consisting of 10μL of the MTT stock solution added to 100 μL of medium is prepared. The plates are incubated at 37°C for 4hr followed by the addition of 100 μL of the SDS–HCl solution to each well and mixing thoroughly using a pipette. The absorbance of each sample is read at 570 nm in an ELISA plate reader. The inhibitory concentration (IC 40) doses are determined using standard procedure [2].Animal Administration:[3]Mice [3]Female A/J mice at 6 weeks of age are used. At 6 weeks of age, mice are fed control irradiated AIN–76A modified diet. At 7 weeks of age, the mice intended for carcinogen treatment receive a single dose of 10 mol (2.07 mg) NNK/mouse by intraperitoneal injection.All mice are weighed once every 2 weeks until termination of the study. Three weeks after NNK treatment, groups of mice (25mice/group) are fed control AIN–76A or experimental diets containing 50 or 100 ppm CP–31398 or 150 or 300 ppm PRIMA–1 untilProduct Name:PRIMA–1Cat. No.:HY-19980A CAS No.:5608-24-2Molecular Formula:C 9H 15NO 3Molecular Weight:185.22Target:MDM–2/p53; Autophagy Pathway:Apoptosis; Autophagy Solubility:DMSO: ≥ 44 mg/mLtermination. Mice are killed by CO2 asphyxiation followed by cervical dislocation after 17 weeks (10 mice/group) or 34 weeks (15 mice/group) of exposure to test agents. At the time of sacrifice, lungs are lavaged, perfused, and fixed in phosphate–buffered formalin, transferred within 2 days to 70% alcohol, and evaluated under a dissecting microscope for the number of tumors and tumor size. Tumors on the lung surface are enumerated by at least two experienced readers, blinded to sample identifiers, using a dissecting microscope. Tumor diameters are measured using Fisher brand digital calipers.References:[1]. Cui B, et al. PRIMA–1, a mutant p53 reactivator, restores the sensitivity of TP53 mutant–type thyroid cancer cells to the histone methylation inhibitor3–Deazaneplanocin A. J Clin Endocrinol Metab. 2014 Jun;99(6):E962–70.[2]. Zhang Z, et al. Targeting cancer stem cells with p53 modulators. Oncotarget. 2016 Apr 8.[3]. Rao CV, et al. Chemopreventive effects of the p53–modulating agents CP–31398 and Prima–1 in tobacco carcinogen–induced lung tumorigenesis in A/J mice. Neoplasia. 2013 Sep;15(9):1018–27.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。
TOK-001_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:TOK–001 is a multifunctional antiandrogen and CYP17 inhibitor (IC 50=47 nM) in castration resistant prostate cancer (CRPC).IC50 & Target: IC50: 47 nM (CYP17)[1]In Vitro: TOK–001 affords strong CYP17 lyase inhibition, with IC 50 of 47 nM [1]. TOK–001 is both a CYP17A1 inhibitor and androgen receptor antagonist and the similarity of these binding modes is likely the reason for this dual mechanism of action.This CYP17A1binds abiraterone and TOK–001 with absorbance decreases at 402 nm and increases at 424 nm, consistent with nitrogen binding to the heme iron (type II interaction) with K d of <100 nM [2]. When LNCaP cells are cultured in medium supplemented withcharcoal–stripped serum (CSS, T<1 nM) followed by treatment with increasing concentrations of TOK–001, the steady–state levels of AR protein are markedly decreased (up to 84%, 15 μM TOK–001). In LAPC–4 cells, abiraterone alcohol reduced AR expression to a greater extent than TOK–001 at concentrations greater than or equal to 1 μM. When LNCaP cells are treated with 20 μM TOK–001for 24 h, AR mRNA levels are reduced by 38%[3].In Vivo: Mice inoculated with LAPC–4 tumors are treated subcutaneously with 0.15 mmol/kg of TOK–001 twice daily. Mice treated with TOK–001 have smaller average tumor volume on day 31 when compared to control (p= 0.0001). TOK–001 treatment alsosignificantly reduces the growth rate of tumor growth compared to control (p<0.0001). Upon excision, final tumor weights are also significantly reduced in animals treated with TOK–001 compared to animals treated with control, and castration (p<0.05)[1].PROTOCOL (Extracted from published papers and Only for reference)Kinase Assay:[2]Progesterone 17α–hydroxylation is evaluated using a modified HPLC method with UV–detection. CYP17A1 (50 pmol)and rat NADPH–cytochrome P450 reductase 1:4 are mixed, incubated on ice (20 minutes), and added to buffer (50 mM Tris, pH 7.4and 5 mM MgCl 2) containing progesterone (0–50 μM) to a total volume of 500 μL. Phosphatidylcholine (25 μg) is included for side–by–side kinetic comparisons with the full–length enzyme. For IC 50 determinations, inhibitors concentrations are 0–1500 nM for abiraterone and 0–3000 nM for TOK–001 (Shanghai Haoyuan Chemexpress Co., Shanghai, China). After warming (37°C, 3 minutes),reactions are initiated by NADPH addition (20 μL 25 mM), incubated for 10 minutes (37°C), and quenched with 20% trichloroacetic acid (300 μL) and placed on ice. The 17α–hydroxyprogesterone metabolite is identified by UV detection at 248 nm following HPLC separation and coeluted with authentic standards. The HPLC mobile phase is 40% acetonitrile, 60% water with 1% acetic acid and run at 1 mL/min (Phenomenex, Luna 5 μ, C18, 50×4.6 mm)[2].Cell Assay: TOK–001 is dissolved with DMSO and diluted with appropriate media [3].[3]LNCaP cells are seeded in 24–well plates at 70% confluence a day before transfections. Cells then are transfected with plasmid DNA (0.5 μg/well) carrying pIR–AR 5′UTR–Luc (5′UTR; test) or pIRES–Luc (IRES, control) for 6 h in serum–free and antibiotic–free conditions. Transcription of both luciferasereporter genes is under the control of the CMV promoter. Lipofectamine 2000 reagent is used in all transfections according to the manufacturer's instructions. Cells are then treated with doses of TOK–001 (0, 10, and 20 μM) in 5% FBS/T–Medium. Luciferase reporter gene activities are measured using Luciferase Assay System from Promega at 36 h post treatment using a BMG LabtechProduct Name:TOK–001Cat. No.:HY-70006CAS No.:851983-85-2Molecular Formula:C 26H 32N 2O Molecular Weight:388.55Target:Cytochrome P450Pathway:Metabolic Enzyme/Protease Solubility:DMSO: 18 mg/mLmicroplate reader. Relative luciferase units are normalized to total protein and then normalized to vector control (pIR–AR5′UTR–Luc) and the result is presented as luciferase activity. For cell proliferation studies, LNCaP cells in 96–well plate are seeded 24 h prior to drug treatment and then treated with control (mock), TOK–001 (10 μM), or abiraterone alcohol (10 μM) in 5%FBS/T–medium for 72 h. Cell proliferation is determined using MTS[3].Animal Administration: TOK–001 is dissolved in DMSO and then diluted with saline or PBS[1]. [1]Mice[1]Mice inoculated with LAPC–4 tumors are treated subcutaneously with 0.15 mmol/kg of TOK–001 twice daily. Mice treated with TOK–001 have smaller average tumor volume on day 31 when compared to control (p=0.0001). TOK–001 treatment also significantly reduced the growth rate of tumor growth compared to control (p<0.0001). Upon excision, final tumor weights are also significantly reduced in animals treated with TOK–001 compared to animals treated with control, and castration (p<0.05).References:[1]. Bruno RD, et al. Synthesis and biological evaluations of putative metabolically stable analogs of VN/124–1 (TOK–001): head to head anti–tumor efficacy evaluation of VN/124–1 (TOK–001) and abiraterone in LAPC–4 human prostate cancer xenograft model.Steroid[2]. DeVore NM, et al. Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK–001.Nature. 2012 Jan 22;482(7383):116–9.[3]. Soifer HS, et al. Direct regulation of androgen receptor activity by potent CYP17 inhibitors in prostate cancer cells.J Biol Chem. 2012 Feb 3;287(6):3777–87. Epub 2011 Dec 15.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。
人类TAP1基因克隆及表达载体的构建
文章编号:1007-8738(2004)01-0053-02人类T AP1基因克隆及表达载体的构建刘 玉1,李殿俊1,吕雪莹1,杨秋霞1,谷金宇2,王 兰1(哈尔滨医科大学:1免疫学教研室,2附属二院普外科,黑龙江哈尔滨150086)收稿日期:2003-06-16; 修回日期:2003-09-05基金项目:黑龙江省自然科学基金资助课题(No.D0122)作者简介:刘 玉(19762),女,黑龙江五大连池人,助教,硕士生.Tel :(0451)86674566;Email :christineliuyu @关键词:TAP1;基因克隆;表达载体的构建;序列分析中图分类号:Q785 文献标识码:A 抗原处理相关转运体(TAP )属于ABC (A TP 2binding cas 2sette )转运体超家族B 亚家族。
人类TAP 基因位于6号染色体上的MHC 2II 类基因区,其编码的TAP1和TAP2分子,分别由748和686个氨基酸残基所组成,两者可形成异源二聚体参与肽类的转运过程,在MHC 2I 类分子介导的抗原递呈途径中起着重要作用[1,2]。
因此,TAP 的异常将严重影响抗原递呈,成为病毒感染及肿瘤细胞逃避免疫监视的重要机制[3],如卵巢癌[4]、肝癌[5]及宫颈癌[6]细胞中TAP1的表达量明显下降。
我们在本实验中,从B 淋巴母细胞系中克隆出TAP1基因,并构建了其表达载体pcDNA3.1/V52His TOPO TA 2TAP1。
1 材料和方法1.1 材料 人类B 2LC L 细胞由本校生物学教研室惠赠。
TRI 2zol 试剂、Therm oscript RT 2PCR system 及P fx DNA 聚合酶,以及pcDNA 3.1/V52H is TOPO T A 载体,均购自Invitrogen 公司。
CONCEPT 凝胶纯化试剂盒购于G ibcoBRL 公司。
MiniBEST 质粒提取试剂盒及特异性T AP1引物购于T a K aRa 公司。
ATX PI(1%)
很常见（10 %） ；常见（1 % -< 10 %） ；少见（0.1 %-< 1 %） ；罕见（0.01 %-< 0.1 %） ； 非常罕见（包括单个病例，< 0.01 %） 。 免疫系统疾病 非常罕见：过敏性休克、血管性水肿、荨麻疹（全身性） 、哮喘（哮喘发作） 中枢神经系统疾病 非常罕见：脑血管意外、头痛、偏头痛（当用硬化泡沫时，频率为“罕见” ） 、感觉异常 （局部） 、意识丧失、意识模糊状态、眩晕、失语、共济失调、轻偏瘫、口腔感觉减退 眼科疾病 非常罕见（当用硬化泡沫时，频率为“罕见” ） ：视力损害（视觉障碍） 心脏疾病 非常罕见：心脏骤停、心悸、心律失常 血管疾病 常见：新血管形成、血肿 少见：表浅血栓性静脉炎、静脉炎 罕见：深静脉血栓形成（这可能是由于基础疾病） 非常罕见：肺栓塞、血管迷走性晕厥、循环衰竭、血管炎 呼吸、胸和纵膈疾病 非常罕见：呼吸困难、胸部不适（胸部压迫感） 、咳嗽 肠胃道疾病 非常罕见：味觉障碍、恶心、呕吐 皮肤和皮下组织疾病 常见：皮肤色素沉着、瘀斑 少见：过敏性皮炎、接触性荨麻疹、皮肤反应、红斑 非常罕见：多毛症（在硬化治疗区域） 肌肉骨骼系统和结缔组织疾病 罕见：肢端疼痛 一般疾病和给药部位状况 常见：注射部位疼痛（短期） 、注射部位血栓形成（局部静脉曲张内血块） 少见：坏死、硬结、肿胀 非常罕见：发热、潮热、无力、不适 检查 非常罕见：血压异常
2
聚多卡醇对血管内皮有浓度依赖性和体积依赖性损伤作用。静脉曲张硬化治疗后应用压迫 绷带压迫受损静脉壁，以防止过度血栓形成和起初形成的附壁血栓的血管再通。这导致希望的 转化成纤维组织而硬化。此外，聚多卡醇有局麻作用，可局部、可逆性抑制末端感觉器官（感 受器）的兴奋性和感觉神经纤维的传导能力。 毒理研究 药理学安全性研究显示有负性变时、变力和变更神经传导作用，因而血压下降。同时给予 其他局麻药时观察到额外的致心律失常效应。重复给药后，所有受试种属的部分动物显示肠、 肾上腺和肝脏有组织学改变，家兔的肾脏也有变化。聚多卡醇均导致血尿。在 4 mg/kg /天和更 高剂量时，雄性大鼠在连续 7 天每天给药情况下，肝脏重量增加；在 14 mg/kg/天和更高剂量 时，ALAT (GPT) 和 ASAT (GOT)活性升高。 遗传毒性 在体外和体内对聚多卡醇进行检测，除 1 次体外试验可见诱发哺乳动物细胞多倍体，其他 试验均为阴性。但如果正确使用，预期无相关的潜在遗传毒性。 生殖毒性 大鼠连续几周或器官发生期间静脉给予聚多卡醇，未见对雄性或雌性大鼠生育力或早期胚 胎发育的明显影响，未见对大鼠或兔子代生长发育毒性。但在母体毒性剂量范围可见胚胎毒性 和胎仔毒性作用（胚胎 /胎儿死亡率增加，胎儿体重减低）。当在器官发生期间将给药时间限 制为连续 4 天间隔，则既无母体毒性也无胚胎毒性/胎儿毒性作用发生（兔）。大鼠围产期静 脉注射聚多卡醇，未见对子代生长发育、行为和生殖功能的明显影响。聚多卡醇可透过大鼠胎 盘屏障。 【药代动力学】 6 例健康志愿者经大隐静脉接受一次 37 mg
TAPI-1_SDS_MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:May-24-2017Print Date:May-24-20171. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :TAPI-1Catalog No. :HY-16657CAS No. :163847-77-61.2 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:TAPI 1; TAPI1Formula:C26H37N5O5Molecular Weight:499.60CAS No. :163847-77-64. 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:Powder-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 (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 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 2017 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。
DAPT_DataSheet_MedChemExpress
Inhibitors, Agonists, Screening Libraries Data SheetBIOLOGICAL ACTIVITY:DAPT is a γ–secretase inhibitor, reduces the total beta–amyloid peptide (Aβ) production with IC 50 of 20 nM in HEK 293 cells.IC50 & Target: IC50: 20 nM (Aβ, in HEK 293 cells)[1]In Vitro: DAPT inhibits Aβ production over 90%, effects only a modest reduction in APPβ in the culture media. Although APPβ is reduced by about 30% by DAPT treatment, this effect is not concentration–dependent and is reversed by the removal of DAPT [1].CNE–2 cells are treated with increasing concentrations of DAPT (0, 25, 50 and 75 μM), and the γ–secretase–generated Notch 1fragment Val1744–NICD is decreased after 48 h in a dose–dependent manner (P<0.01). The activation of γ–secretase is almost completely inhibited by DAPT at the concentration of 50 μM [2]. In Vivo: DAPT is administered to PDAPP mice (100 mg/kg s.c.) and the levels of DAPT and Aβ are examined in the brain cortex. Peak DAPT levels of 490 ng/g are achieved in the brain 3 h after treatment, and levels greater than 100 ng/g (~200 nM) are sustained throughout the first 18 h. These brain concentrations of DAPT are in excess of its IC 50 for lowering Aβ in neuronal cultures (115 nM),and results in a robust and sustains pharmacodynamic effect [1]. DAPT protects brain against cerebral ischemia by down–regulating the expression of Notch 1 and Nuclear factor kappa B in rats. Western blot analyses also show a significant decrease of Notch 1 andNF–κB expression in DAPT (0.03 mg/kg) group (P<0.05 vs. MCAO group)[3]. PROTOCOL (Extracted from published papers and Only for reference)Cell Assay: DAPT is dissolved in DMSO and stored, and then diluted with appropriate media (DMSO 0.1%) before use [1].[1]Human embryonic kidney cells, transfected with the gene for APP 751 (HEK 293) are used for routine Aβ reduction assays. Cells are plated in 96–well plates and allowed to adhere overnight in Dulbecco's modified Eagle medium (DMEM) supplemented with 10%heat–inactivated fetal bovine serum. Cells are pre–treated for 2 h at 37°C with DAPT (0, 0.4, 2, 10, 50 and 250 nM), media are aspirated off and fresh compound solutions applied. After an additional 2–h treatment period, conditioned media are drawn off and analyzed by a sandwich ELISA (266–3D6) specific for total Aβ. Reduction of Aβ production is measured relative to control cells treated with 0.1% DMSO and expressed as a percentage inhibition. Data from at least six doses in duplicate are fitted to afour–parameter logistical model using XLfit software in order to determine potency [1].Animal Administration: DAPT is formulated in corn oil, 5% (v/v) ethanol (Mice)[1].DAPT is dissolved in 0.01 M PBS including 5% DMSO to prepare concentrations of 8.3 mg/mL (Rat)[3].[1][3]Mice [1]The three– to four–month–old heterozygous PDAPP transgenic mice overexpressing the APP V717F mutant form of the amyloidprecursor protein. Each treatment group (n=10) consists of equal numbers of age–matched male and female animals that are fasted overnight prior to treatment. Both treatment and control groups are dosed at a volume of 10 mL/kg with DAPT or vehicle alone.Tissues are processed and all Aβ and APP measurements are made. After removal of the brain, the cortex from one hemisphere is homogenized, extracted with 5 M guanidine, 50 mM Tris–pH 8.0, centrifuged, and the supernatant is used for Aβ measurements.Cortex from the other hemisphere is snap frozen for analysis of compound levels. Aβ levels are expressed as ng/g of wet tissue weight,Product Name:DAPT Cat. No.:HY-13027CAS No.:208255-80-5Molecular Formula:C 23H 26F 2N 2O 4Molecular Weight:432.46Target:γ–secretase; γ–secretase; Autophagy Pathway:Stem Cell/Wnt; Neuronal Signaling; Autophagy Solubility:DMSO: ≥ 215 mg/mLand percentage reductions are calculated relative to the mean Aβ level of tissue from vehicle–treated control animals. Data are analyzed with Mann–Whitney non–parametric statistics to assess significance.Rat[3]Male Sprague–Dawley rats (260–290 g) are used. DAPT solution is stereotactically injected into the lateral cerebral ventricle (LV) immediately after MCAO. The stereotactic injections into the LVs are performed at coordinates -0.8 mm anteroposterior, ±1.5 mm mediolateral and -4.5 mm dorsoventral from the bregma. 30 rats are randomly assigned to three operating groups (10 rats in each group): sham–operated group that receive equal volume of PBS without MCAO operation; MCAO group that receive equal volume PBS after MCAO (MCAO); and DAPT group that receive DAPT as 0.03 mg/kg after MCAO. 24 h after operation the first neurological function is assessed and then 48 h after operation the second neurological function is assessed. Meanwhile, brain water content and infarction volume are measured and compared among different groups.References:[1]. Dovey HF, et al. Functional gamma–secretase inhibitors reduce beta–amyloid peptide levels in brain. J Neurochem. 2001 Jan;76(1):173–81.[2]. Zhou JX, et al. γ–secretase inhibition combined with cisplatin enhances apoptosis of nasopharyngeal carcinoma cells.Exp Ther Med. 2012 Feb;3(2):357–361.[3]. Li S, et al. DAPT protects brain against cerebral ischemia by down–regulating the expression of Notch 1 and nuclear factor κB in rats. Neurol Sci. 2012 Dec;33(6):1257–64.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。
IPI549-SDS-MedChemExpress
Inhibitors, Agonists, Screening LibrariesSafety Data Sheet Revision Date:Oct.-12-2018Print Date:Oct.-12-20181. PRODUCT AND COMPANY IDENTIFICATION1.1 Product identifierProduct name :IPI549Catalog No. :HY-100716CAS No. :1693758-51-81.2 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 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), H4132.2 GHS Label elements, including precautionary statementsPictogramSignal word No data availableHazard statement(s)H302 Harmful if swallowed.H413 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 you feel unwell.P333 Rinse mouth.2.3 Other hazardsNone.3. COMPOSITION/INFORMATION ON INGREDIENTS3.1 SubstancesSynonyms:IPI-549;IPI 549Formula:C30H24N8O2Molecular Weight:528.56CAS No. :1693758-51-84. 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:Powder-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 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 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.IMDGUN number: 3077Class: 12Packing group: IIIEMS-No: F-A, S-FProper shipping name: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S.Marine pollutant: Marine pollutantIATAUN number: 3077Class: 12Packing group: IIIProper shipping name: Environmentally hazardous substance, solid, n.o.s.15. REGULATORY INFORMATIONSARA 302 Components:No chemicals in this material are subject to the reporting requirements of SARA Title III, Section 302.SARA 316 Components:This material does not contain any chemical components with known CAS numbers that exceed thethres33&33U_HKSCS33&MingLiU_HKSCS3333333333316. 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。
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Inhibitors, Agonists, Screening Libraries
Data Sheet
BIOLOGICAL ACTIVITY:
TAPI–1 is a specific TACE (TNF–α–converting enzyme) inhibitor.
IC50 value:
Target:
TAPI–1 inhibited LL–37–induced TGF–α production, EGFR activation and subsequent MUC5AC mucin production, whereas
TGF–α–neutralizing antibody, but not AR– or HB–EGF–neutralizing antibody, inhibited LL–37–induced EGFR activation and subsequent MUC5AC mucin production in NCI–H292 cells [1]. Using the TNF–alpha converting enzyme (TACE) inhibitor, TAPI–1, TPA–stimulated TNFalpha shedding could be completely prevented in PKCepsilon transgenic mice and isolated keratinocytes [2]. Pretreatment with antibody against FcγRII or with CD32 siRNA, p47(phox) siRNA, apocynin, N–acetylcysteine, tumor necrosis factor–α protease inhibitor 1 (TAPI–1) or TACE siRNA attenuated sLOX–1 release induced by CRP. CRP also elevated serum sLOX–1 levels in a rabbit model of atherosclerosis [3].
PROTOCOL (Extracted from published papers and Only for reference)
Cell assay [3]
Peripheral blood samples were obtained from six normal subjects and six patients with ACS after their informed consent. Peripheral blood mononuclear cells (PBMC) were isolated by Ficoll density gradient centrifugation and cultured in RPMI 1640 medium with 20%autologous serum at 37°C in 5% CO2 for seven days to induce differentiation into macrophages. Then macrophages from PBMCs were stimulated similarly to the macrophages from THP–1 cells but without TNF–α treatment. Cell–free supernatants were harvested and kept at –80°C for cytokine measurements.
Animal administration [3]
Twenty New Zealand white rabbits, 8 weeks old, underwent balloon–induced endothelial injury in the abdominal aorta after being anesthetized with 3% pentobarbital sodium (30 mg/kg). They were fed a 0.5% cholesterol diet for 12 weeks to establish an animal model of atherosclerosis as described previously (13). At the end of week 12, rabbits were fasted for 24 h and randomly divided into group A (n = 10) and group B (n = 10). Group A received intravenous injection of human recombinant CRP (3 mg/kg), and group B received intravenous injection of saline. Blood samples were obtained 6 h after injection, and levels of human CRP in the serum were measured by a highly sensitive nephelometric assay. The experiment complied with the Animal Management Rule of the Ministry of Public Health, People's Republic of China (documentation 55, 2001) and was approved by the Animal Care Committee of Shandong University.
References:
[1]. Zhang Y, et al. The human Cathelicidin LL–37 induces MUC5AC mucin production by airway epithelial cells via TACE–TGF–α–EGFR pathway. Exp Lung Res.
Product Name:
TAPI–1Cat. No.:
HY-16657CAS No.:
163847-77-6Molecular Formula:
C 26H 37N 5O 5Molecular Weight:
499.60Target:
MMP Pathway:
Metabolic Enzyme/Protease Solubility:
DMSO: ≥ 31 mg/mL
2014 Jun 5.
[2]. Wheeler DL, et al. Protein kinase Cepsilon is linked to 12–O–tetradecanoylphorbol–13–acetate–induced tumor necrosis factor–alpha ectodomain shedding and the development of metastatic squamous cell carcinoma in protein kinase Cepsilon transgenic mice. Cancer Res. 2003 Oct 1;63(19):6547–55.
[3]. Zhao XQ, et al. CRP enhances soluble LOX–1 release from macrophages by activating TNF–α converting enzyme. J Lipid Res. 2011 May;52(5):923–33.
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。