660868-91-7

• 常用中文名：3-[2-(三氟甲基)苄氧基]-5-(5,6-二甲氧基-1H-苯并[d]咪唑-1-基)-2-噻吩甲酰胺
• 常用英文名：GW843682X
• CAS号：660868-91-7
• 分子式：C₂₂H₁₈F₃N₃O₄S
• 分子量：477.46
• 相关类别： 信号通路 细胞周期/DNA损伤 Polo样激酶(PLK)
• 发布时间：2018-08-26 17:50:07
• 更新时间：2024-01-10 09:34:08
• GW843682X 是一种选择性的,ATP-竞争性的 PLK1 and PLK3 抑制剂,IC50 值分别为 2.2 nM and 9.1 nM,选择性是其他 30 种激酶的 100 多倍。

名称

• 中文名: 3-[2-(三氟甲基)苄氧基]-5-(5,6-二甲氧基-1H-苯并[d]咪唑-1-基)-2-噻吩甲酰胺
• 英文名: 5-(5,6-dimethoxybenzimidazol-1-yl)-3-[[2-(trifluoromethyl)phenyl]methoxy]thiophene-2-carboxamide
• 中文别名: 5-(5,6-二甲氧基-1H-苯并咪唑-1-基)-3-[[2-(三氟甲基)苯基]甲氧基]-2-噻吩羧胺
• 英文别名: thiophene deriv.,20; Kinome_3462; GW 843682X; 5-(5,6-Dimethoxy-1H-benzimidazol-1-yl)-3-{2-[2-(trifluoromethyl)phenyl]ethoxy}-2-thiophenecarboxamide; 2-Thiophenecarboxamide, 5-(5,6-dimethoxy-1H-benzimidazol-1-yl)-3-[2-[2-(trifluoromethyl)phenyl]ethoxy]-; GW843682X

物化性质

• 密度: 1.4±0.1 g/cm3
• 沸点: 629.6±65.0 °C at 760 mmHg
• 分子式: C₂₂H₁₈F₃N₃O₄S
• 分子量: 477.46
• 闪点: 334.6±34.3 °C
• PSA: 116.84000
• LogP: 4.25
• 蒸汽压: 0.0±1.8 mmHg at 25°C
• 折射率: 1.613
• 储存条件: 2-8℃

生物活性

• 描述: GW843682X 是一种选择性的,ATP-竞争性的 PLK1 and PLK3 抑制剂,IC50 值分别为 2.2 nM and 9.1 nM,选择性是其他 30 种激酶的 100 多倍。
• 相关类别:
  信号通路 >> 细胞周期/DNA损伤 >> Polo样激酶(PLK)
  研究领域 >> 癌症
• 靶点:

  PLK1:2.2 nM (IC50)

  PLK3:9.1 nM (IC50)

  PDGFR1β:160 nM (IC50)

  VEGFR2:360 nM (IC50)

  Aurora A:4800 nM (IC50)

  CDK2/cyclin A:7600 nM (IC50)

• 体外研究: GW843682X(化合物1)对抑制肿瘤细胞生长有效,对于A549,BT474,HeLa,H460和HCT116细胞系,IC50为0.41,0.57,0.11,0.38和0.70μM。 GW843682X剂量依赖性地抑制Ser15-p53的PLK1磷酸化,IC50为0.14μM。 GW843682X(3μM)在处理24,48和72小时后在HDF细胞和H460细胞中引起强烈的G2-M抗体。 GW843682X(5μM)导致H460细胞而非HDF细胞凋亡[1]。 GW843682X抑制U937细胞增殖,EC50为120 nM。 GW843682X(500 nM)与5μMVP-16联合可抑制50％的U937细胞进入有丝分裂[2]。 GW843682X(0.06-1μM)具有抑制急性白血病细胞增殖的活性,并增强长春新碱的抗增殖活性。此外,GW843682X(0.1-1μM)以剂量和时间依赖性方式诱导白血病细胞凋亡。 GW843682X(0.5-1μM)使白血病细胞中的Bcl-x1去磷酸化[3]。
• 激酶实验: PLK1和PLK3蛋白质由杆状病毒感染的粉纹夜蛾（Trichoplusia ni）细胞制备。 PLK1和PLK3的酶活性测定如下。所有测量均在信号产生随时间和酶线性增加的条件下获得。将测试化合物加入到白色384孔测定板（0.1μL，10μL和一些20μL测定，1μL，对于一些20μL测定）中，在100％DMSO中以可变的已知浓度。 DMSO（1-5％终浓度）和EDTA（65mM）用作对照。反应混合物在22℃下含有下列组分：25mM HEPES（pH7.2）; 15mM MgCl2; 1μMATP; 0.05μCi/孔[γ-33P] ATP（10Ci / mmol）; 1μM底物肽（Biotin-Ahx-SFNDTLDFD）; 0.15 mg / mL牛血清白蛋白; 1 mM DTT;和2nM PLK1激酶结构域或5nM全长PLK3。通过自动液体处理器加入酶后立即将反应混合物（10或20μL）快速加入每个孔中，并在22℃温育1至1.5小时。每孔用50μL终止混合物[50mM EDTA，4.0mg / mL链霉抗生物素蛋白SPA珠粒在Dulbecco PBS（不含Mg 2+和Ca 2+），50μMATP]中终止20μL酶促反应。每孔用10μL终止混合物[50mM EDTA，3.0mg / mL链霉抗生物素蛋白偶联SPA成像Beadsin Dulbecco's PBS（不含Mg 2+和Ca 2+），50μMATP）终止10μL反应。将板密封，以500×g旋转1分钟或静置过夜，并在Packard TopCount中计数30秒/孔或用Viewlux成像仪成像。将高于背景的信号（EDTA对照）转化为相对于在对照（仅DMSO）孔中获得的抑制百分比[1]。
• 细胞实验: 进行分析并分析数据。在这些测定中，H460细胞以每孔2,000个的密度接种，HDF细胞以每孔5,000个接种，耐药细胞系MES-SA / DX5及其敏感的亲本系MES-SA以7,000接种。 96孔板中每孔6,000个。这些密度允许载体对照在3天测定过程中以对数方式生长。将所有细胞暴露于含有5％FBS，50μg/ mL庆大霉素和0.3％（v / v）DMSO（HDF细胞）的低葡萄糖DMEM中的3倍稀释的化合物（30-0.00152μM）; RPMI 1640含有5％FBS，50μg/ mL庆大霉素和0.3％（v / v）DMSO（H460）;或McCoy的5A含有5％FBS，50μg/ mL庆大霉素和0.3％（v / v）DMSO（MES-SA和MES-SA / DX5）[1]。
• 参考文献:

  [1]. Lansing TJ, et al. In vitro biological activity of a novel small-molecule inhibitor of polo-like kinase 1. Mol Cancer Ther. 2007 Feb;6(2):450-9. Epub 2007 Jan 31.

  [2]. Didier C, et al. Evaluation of Polo-like Kinase 1 inhibition on the G2/M checkpoint in Acute Myelocytic Leukaemia. Eur J Pharmacol. 2008 Sep 4;591(1-3):102-5.

  [3]. Ikezoe T, et al. A novel treatment strategy targeting polo-like kinase 1 in hematological malignancies. Leukemia. 2009 Sep;23(9):1564-76.

MSDS

Section1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE Product identifiers Product name: GW843682X CAS-No.: 660868-91-7 Relevant identified uses of the substance or mixture and uses advised against Identified uses: Laboratory chemicals, Manufacture of substances Section2. HAZARDS IDENTIFICATION Classification of the substance or mixture Classification according to Regulation (EC) No 1272/2008 [EU-GHS/CLP] Skin irritation (Category 2) Eye irritation (Category 2) Specific target organ toxicity - single exposure (Category 3) Chronic aquatic toxicity (Category 4) Classification according to EU Directives 67/548/EEC or 1999/45/EC Irritating to eyes, respiratory system and skin. Label elements Labelling according Regulation (EC) No 1272/2008 [CLP] Pictogram Signal wordWarning Hazard statement(s) H315Causes skin irritation. H319Causes serious eye irritation. H335May cause respiratory irritation. H413May cause long lasting harmful effects to aquatic life. Precautionary statement(s) P261Avoid breathing dust/ fume/ gas/ mist/ vapours/ spray. P305 + P351 + P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. Supplemental Hazardnone Statements According to European Directive 67/548/EEC as amended. Hazard symbol(s) R-phrase(s) R36/37/38Irritating to eyes, respiratory system and skin. S-phrase(s) S26In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S36/37Wear suitable protective clothing and gloves. Other hazards - none Section3. COMPOSITION/INFORMATION ON INGREDIENTS Substances Synonyms: GW843682 5-(5,6-Dimethoxy-1H-benzimidazol-1-yl)-3-{[2-(trifluoromethyl)- benzyl]oxy}thiophene-2-carboxamide Formula: C22H18F3N3O4S Molecular Weight: 477,46 g/mol ComponentConcentration GW843682X CAS-No.660868-91-7- Section4. FIRST AID MEASURES Description of first aid measures General advice Consult a physician. Show this safety data sheet to the doctor in attendance. If inhaled If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician. In case of skin contact Wash off with soap and plenty of water. Consult a physician. In case of eye contact Rinse thoroughly with plenty of water for at least 15 minutes and consult a physician. If swallowed Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician. Most important symptoms and effects, both acute and delayed To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly investigated. Indication of any immediate medical attention and special treatment needed no data available Section5. FIREFIGHTING MEASURES Extinguishing media Suitable extinguishing media Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide. Special hazards arising from the substance or mixture Carbon oxides, nitrogen oxides (NOx), Sulphur oxides, Hydrogen fluoride Advice for firefighters Wear self contained breathing apparatus for fire fighting if necessary. Further information no data available Section6. ACCIDENTAL RELEASE MEASURES Personal precautions, protective equipment and emergency procedures Use personal protective equipment. Avoid dust formation. Avoid breathing vapors, mist or gas. Ensure adequate ventilation. Evacuate personnel to safe areas. Avoid breathing dust. Environmental precautions Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. Methods and materials for containment and cleaning up Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed containers for disposal. Reference to other sections For disposal see section 13. Section7. HANDLING AND STORAGE Precautions for safe handling Avoid contact with skin and eyes. Avoid formation of dust and aerosols. Provide appropriate exhaust ventilation at places where dust is formed. Conditions for safe storage, including any incompatibilities Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature: 2 - 8 °C Specific end uses no data available Section8. EXPOSURE CONTROLS/PERSONAL PROTECTION Control parameters Components with workplace control parameters Exposure controls Appropriate engineering controls Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and at the end of workday. Personal protective equipment Eye/face protection Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). Skin protection Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and the standard EN 374 derived from it. Body Protection impervious clothing, The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. Respiratory protection For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). Section9. PHYSICAL AND CHEMICAL PROPERTIES Information on basic physical and chemical properties a) AppearanceForm: solid b) Odourno data available c) Odour Thresholdno data available d) pHno data available e) Melting point/freezingno data available point f) Initial boiling point and no data available boiling range g) Flash pointno data available h) Evaporation rateno data available i) Flammability (solid, gas) no data available j) Upper/lowerno data available flammability or explosive limits k) Vapour pressureno data available l) Vapour densityno data available m) Relative densityno data available n) Water solubilityno data available o) Partition coefficient: n- log Pow: 4,797 octanol/water p) Autoignitionno data available temperature q) Decompositionno data available temperature r) Viscosityno data available s) Explosive propertiesno data available t) Oxidizing propertiesno data available Other safety information no data available Section10. STABILITY AND REACTIVITY Reactivity no data available Chemical stability no data available Possibility of hazardous reactions no data available Conditions to avoid no data available Incompatible materials Strong oxidizing agents Hazardous decomposition products Other decomposition products - no data available Section11. TOXICOLOGICAL INFORMATION Information on toxicological effects Acute toxicity no data available Skin corrosion/irritation no data available Serious eye damage/eye irritation no data available Respiratory or skin sensitization no data available Germ cell mutagenicity no data available Carcinogenicity IARC:No component of this product present at levels greater than or equal to 0.1% is identified as probable, possible or confirmed human carcinogen by IARC. Reproductive toxicity no data available Specific target organ toxicity - single exposure Inhalation - May cause respiratory irritation. Specific target organ toxicity - repeated exposure no data available Aspiration hazard no data available Potential health effects InhalationMay be harmful if inhaled. Causes respiratory tract irritation. IngestionMay be harmful if swallowed. SkinMay be harmful if absorbed through skin. Causes skin irritation. EyesCauses serious eye irritation. Signs and Symptoms of Exposure To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly investigated. Additional Information RTECS: Not available Section12. ECOLOGICAL INFORMATION Toxicity no data available Persistence and degradability no data available Bioaccumulative potential no data available Mobility in soil no data available Results of PBT and vPvB assessment no data available Other adverse effects no data available Section13. DISPOSAL CONSIDERATIONS Waste treatment methods Product Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber. Contaminated packaging Dispose of as unused product. Section14. TRANSPORT INFORMATION UN number ADR/RID: -IMDG: -IATA: - UN proper shipping name ADR/RID: Not dangerous goods IMDG: Not dangerous goods IATA:Not dangerous goods Transport hazard class(es) ADR/RID: -IMDG: -IATA: - Packaging group ADR/RID: -IMDG: -IATA: - Environmental hazards ADR/RID: noIMDG Marine pollutant: noIATA: no Special precautions for user no data available SECTION 15 - REGULATORY INFORMATION N/A SECTION 16 - ADDITIONAL INFORMATION N/A

安全

• 符号: GHS07
• 信号词: Warning
• 危害声明: H315-H319-H335-H413
• 警示性声明: P261-P305 + P351 + P338
• 个人防护装备: dust mask type N95 (US);Eyeshields;Gloves
• 危害码 (欧洲): Xi
• 风险声明 (欧洲): R36/37/38
• 安全声明 (欧洲): S26-S36/37
• 危险品运输编码: NONH for all modes of transport