1080622-86-1

• 常用中文名：1-(6,7-二甲氧基-4-喹唑啉基)-3-(2-吡啶基)-1H-1,2,4-三唑-5-胺
• 常用英文名：CP-466722
• CAS号：1080622-86-1
• 分子式：C₁₇H₁₅N₇O₂
• 分子量：349.347
• 相关类别： 生物化工 抑制剂 DNA损伤(DNA Damage) ATM/ATR 抑制剂
• 发布时间：2018-12-10 19:02:45
• 更新时间：2024-01-02 06:59:39
• CP-466722 是一种可逆的 ATM 抑制剂,IC50 值为 4.1 μM,但对 PI3K,PIKK 家族蛋白没有作用。

名称

• 中文名: 1-(6,7-二甲氧基-4-喹唑啉基)-3-(2-吡啶基)-1H-1,2,4-三唑-5-胺
• 英文名: 2-(6,7-dimethoxyquinazolin-4-yl)-5-pyridin-2-yl-1,2,4-triazol-3-amine
• 英文别名: 1H-1,2,4-Triazol-5-amine, 1-(6,7-dimethoxy-4-quinazolinyl)-3-(2-pyridinyl)-; S2245_Selleck; HMS3265A20; 1-(6,7-Dimethoxy-4-quinazolinyl)-3-(2-pyridinyl)-1H-1,2,4-triazol-5-amine; cc-85; HMS3265A19; HMS3265B19; CP466722; CP-466722

物化性质

• 密度: 1.5±0.1 g/cm3
• 沸点: 642.3±65.0 °C at 760 mmHg
• 分子式: C₁₇H₁₅N₇O₂
• 分子量: 349.347
• 闪点: 342.2±34.3 °C
• 精确质量: 349.128723
• PSA: 114.59000
• LogP: 0.83
• 外观性状: white to beige
• 蒸汽压: 0.0±1.9 mmHg at 25°C
• 折射率: 1.737
• 储存条件: 2-8°C
• 水溶解性: DMSO: soluble0.5mg/mL, clear (warmed)

生物活性

• 描述: CP-466722 是一种可逆的 ATM 抑制剂,IC50 值为 4.1 μM,但对 PI3K,PIKK 家族蛋白没有作用。
• 相关类别:
  信号通路 >> 细胞周期/DNA损伤 >> ATM/ATR
  信号通路 >> PI3K/Akt/mTOR 信号通路 >> ATM/ATR
  研究领域 >> 癌症
• 靶点:

  ATM:4.1 μM (IC50)

• 体外研究: CP-466722(CP466722,6-10μM)抑制IR诱导的ATM激酶活性,并且抑制可以快速且完全逆转。 CP466722(6,10μM)抑制小鼠细胞中p53诱导和ATM依赖性磷酸化,但CP466722不能抑制Chk1的ATR活性和ATR依赖性磷酸化。 CP466722(6μM)破坏细胞中依赖ATM的细胞周期检查点[1]。 CP466722(1μM)完全抑制MCF7细胞中的ATM依赖性磷酸化。 CP466722(10μM)可降低MCF7细胞中的pKAP1磷酸化,IC50为0.41μM。 CP466722(10μM)抑制pATM和pKAP1信号[2]。 CP-466722(CP466722,5-50μM)比MCF-7癌细胞更强烈地抑制SKBr-3癌细胞的增殖。 CP466722(10μM)在处理48小时后也略微增加了G1期MCF-7和SKBr-3细胞的比例[3]。
• 激酶实验: 为了筛选ATM激酶活性的小分子抑制剂，进行体外激酶测定，并开发ELISA测定法，其测量ATM下游靶标p53的磷酸化状态。纯化重组GST-p53（1-101）和全长Flag标记的ATM和ATR用于ELISA和体外激酶测定。简言之，将Nunc 96孔Maxisorp板用PBS中的2μg纯化的重组GST-p53（1-101）包被过夜（4℃）。所有后续孵育均在室温下进行。将板洗涤（0.05％v / v-Tween / PBS），然后加入纯化的重组全长ATM激酶（30-60ng），最终体积为80μL反应缓冲液（20mM HEPES，50mM NaCl2，在化合物存在或不存在下，10mM MgCl 2,10mM MnCl 2,1mM DTT和1μMATP）。将包括CP-466722（10μM）的化合物一式两份加入板中，并孵育激酶测定法（90分钟）。洗涤平板（0.05％v / v-吐温/ PBS），封闭（1小时，1％w / v-BSA / PBS）并在抗磷酸化（Ser15）-p53抗体（1：1000 / PBS）之前冲洗。加入板中并孵育（1小时）。为了减少非特异性结合板，在用HRP缀合的山羊抗兔IgG二抗（1：5000 / PBS）温育（1小时）之前洗涤（0.05％v / v-Tween / PBS）。用TMB底物试剂检测与磷酸化GST-p53（1-101）蛋白连接的二抗。开发平板（15-30分钟）并在确定吸光度（λ450nm）之前停止反应（1M H 2 SO 4终浓度）。在ELISA测定中抑制ATM激酶活性的化合物的特征在于使用体外激酶测定法抑制ATM / ATR激酶。使用抗磷酸化（Ser15）-p53抗体的Western印迹用作ATM / ATR抑制的读数[1]。
• 细胞实验: 将细胞一式三份（40,000个细胞/板）铺板，根据需要孵育，然后将培养基和胰蛋白酶消化的细胞组合并测定活力：Vi-CELL TM XR细胞活力分析仪[1]。
• 参考文献:

  [1]. Rainey MD, et al. Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation. Cancer Res. 2008 Sep 15;68(18):7466-74.

  [2]. Guo K, et al. Development of a cell-based, high-throughput screening assay for ATM kinase inhibitors. J Biomol Screen. 2014 Apr;19(4):538-46.

  [3]. Węsierska-Gądek J, et al. Interactions Between Ataxia Telangiectasia Mutated Kinase Inhibition, Poly(ADP-ribose) Polymerase-1 Inhibition and BRCA1 Status in Breast Cancer Cells. J Cancer Prev. 2014 Jun;19(2):125-36.

MSDS

SECTION 1: Identification of the substance/mixture and of the company/undertaking Product identifiers Product name: CP466722 REACH No.: A registration number is not available for this substance as the substance or its uses are exempted from registration, the annual tonnage does not require a registration or the registration is envisaged for a later registration deadline. CAS-No.: 1080622-86-1 Relevant identified uses of the substance or mixture and uses advised against Identified uses: Laboratory chemicals, Manufacture of substances SECTION 2: Hazards identification Classification of the substance or mixture Classification according to Regulation (EC) No 1272/2008 Acute toxicity, Oral (Category 4), H302 For the full text of the H-Statements mentioned in this Section, see Section 16. Classification according to EU Directives 67/548/EEC or 1999/45/EC Xn HarmfulR22 For the full text of the R-phrases mentioned in this Section, see Section 16. Label elements Labelling according Regulation (EC) No 1272/2008 Pictogram Signal wordWarning Hazard statement(s) H302Harmful if swallowed. Precautionary statement(s)none Supplemental Hazardnone Statements Other hazards This substance/mixture contains no components considered to be either persistent, bioaccumulative and toxic (PBT), or very persistent and very bioaccumulative (vPvB) at levels of 0.1% or higher. SECTION 3: Composition/information on ingredients Substances Synonyms: 1-(6,7-Dimethoxy-4-quinazolinyl)-3-(2-pyridinyl)-1H-1,2,4-Triazol-5-amine Formula: C17H15N7O2 Molecular weight: 349,35 g/mol CAS-No.: 1080622-86-1 Hazardous ingredients according to Regulation (EC) No 1272/2008 ComponentClassificationConcentration CP466722 CAS-No.1080622-86-1Acute Tox. 4; H30250 - 100 % Hazardous ingredients according to Directive 1999/45/EC ComponentClassificationConcentration CP466722 CAS-No.1080622-86-1Xn, R22<= 100 % For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16 SECTION 4: 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 Flush eyes with water as a precaution. 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 The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in section 11 Indication of any immediate medical attention and special treatment needed No data available SECTION 5: 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 No data available Advice for firefighters Wear self-contained breathing apparatus for firefighting if necessary. Further information No data available SECTION 6: Accidental release measures Personal precautions, protective equipment and emergency procedures Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation. Avoid breathing dust. For personal protection see section 8. Environmental precautions Do not let product enter drains. 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. SECTION 7: 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. For precautions see section 2.2. 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 Storage class (TRGS 510): Non Combustible Solids Specific end use(s) Apart from the uses mentioned in section 1.2 no other specific uses are stipulated SECTION 8: 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 Complete suit protecting against chemicals, 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). Control of environmental exposure Do not let product enter drains. SECTION 9: 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: 2,339 octanol/water p) Auto-ignitionNo 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 SECTION 10: Stability and reactivity Reactivity No data available Chemical stability Stable under recommended storage conditions. 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 In the event of fire: see section 5 SECTION 11: 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 sensitisation 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 No data available Specific target organ toxicity - repeated exposure No data available Aspiration hazard No data available Additional Information RTECS: Not available To the best of our knowledge, the chemical, physical, and toxicological properties have not been thoroughly investigated. SECTION 12: 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 This substance/mixture contains no components considered to be either persistent, bioaccumulative and toxic (PBT), or very persistent and very bioaccumulative (vPvB) at levels of 0.1% or higher. Other adverse effects No data available SECTION 13: 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. SECTION 14: 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 This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006. Safety, health and environmental regulations/legislation specific for the substance or mixture No data available Chemical Safety Assessment For this product a chemical safety assessment was not carried out SECTION 16: Other information Full text of H-Statements referred to under sections 2 and 3. Acute Tox.Acute toxicity H302Harmful if swallowed. Full text of R-phrases referred to under sections 2 and 3 Xn Harmful R22 Harmful if swallowed. Further information Copyright 2014 Co. LLC. License granted to make unlimited paper copies for internal use only. The above information is believed to be correct but does not purport to be all inclusive and shall be used only as a guide. The information in this document is based on the present state of our knowledge and is applicable to the product with regard to appropriate safety precautions. It does not represent any guarantee of the properties of the product. Corporation and its Affiliates shall not be held liable for any damage resulting from handling or from contact with the above product. See and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

安全

• 符号: GHS07
• 信号词: Warning
• 危害声明: H302
• 危害码 (欧洲): Xn
• 风险声明 (欧洲): 22
• 危险品运输编码: NONH for all modes of transport