418805-02-4

• 常用中文名：4-[4-[(5-硝基-2-呋喃基)亚甲基]-3,5-二氧代-1-吡唑烷基]苯甲酸乙酯
• 常用英文名：PYR-41
• CAS号：418805-02-4
• 分子式：C₁₇H₁₃N₃O₇
• 分子量：371.301
• 相关类别： 生物化工 抑制剂 泛素化抑制剂(Ubiquitin) E1 Activating 抑制剂
• 发布时间：2017-10-27 16:48:05
• 更新时间：2024-01-10 19:53:27
• PYR-41 是一种特异的,细胞可透过的 E1 抑制剂,IC50 值 < 10 μM。

名称

• 中文名: 4-[4-[(5-硝基-2-呋喃基)亚甲基]-3,5-二氧代-1-吡唑烷基]苯甲酸乙酯
• 英文名: ethyl 4-[(4Z)-4-[(5-nitrofuran-2-yl)methylidene]-3,5-dioxopyrazolidin-1-yl]benzoate
• 英文别名: Ethyl 4-{(4Z)-4-[(5-nitro-2-furyl)methylene]-3,5-dioxo-1-pyrazolidinyl}benzoate; 4[4-(5-Nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester; Benzoic acid, 4-[(4Z)-4-[(5-nitro-2-furanyl)methylene]-3,5-dioxo-1-pyrazolidinyl]-, ethyl ester; PYR-41

物化性质

• 密度: 1.5±0.1 g/cm3
• 分子式: C₁₇H₁₃N₃O₇
• 分子量: 371.301
• 精确质量: 371.075348
• PSA: 134.67000
• LogP: 2.87
• 外观性状: red to brown
• 折射率: 1.652
• 储存条件: ?20°C
• 水溶解性: Soluble in DMSO at 5mg/ml with warming

生物活性

• 描述: PYR-41 是一种特异的,细胞可透过的 E1 抑制剂,IC50 值 < 10 μM。
• 相关类别:
  信号通路 >> 代谢酶/蛋白酶 >> E1/E2/E3酶
  研究领域 >> 癌症
• 靶点:

  IC50: < 10 μM (E1)

• 体外研究: 除阻断泛素化外,PYR-41还增加细胞中的总SUMO化。 PYR-41减弱细胞因子介导的核因子-κB活化。 PYR-41还可以防止IκBα的下游泛素化和蛋白酶体降解。此外,PYR-41抑制p53的降解并激活该肿瘤抑制因子的转录活性[1]。 PYR-41(50μM)促进泛素化蛋白质的积累。 PYR-41在4小时后引起Z138细胞中DUB活性的浓度依赖性(10-50μM)下降。即使在最低浓度(10μM)下,PYR-41也有效抑制USP5 DUB活性。 PYR-41有效(10-50μM)抑制各种DUB的活性,确定代表USP9x,USP5,USP14,UCH37和UCH-L3。用DTT和PYR-41共同处理Z138细胞完全消除了泛素化蛋白的积累[2]。
• 激酶实验: 将兔或小鼠E1（apper 250ng）与32P-遍在蛋白在1x反应缓冲液[50mM Tris（pH 7.4），0.2mM ATP，0.5mM MgCl 2]中在室温下孵育15分钟。在一些实验中，His标记的小鼠E1在进行温育和反应之前与TALON钴亲和树脂结合。将小鼠E1和32P-遍在蛋白加入到1x反应缓冲液中的珠子中，并如E1反应一样温育。将样品在非还原性SDS-PAGE样品缓冲液中加热，并通过SDS-PAGE分离。具有遍在蛋白的硫酯通过Storm PhosphoImager可视化。
• 参考文献:

  [1]. Yang Y, et al. Inhibitors of ubiquitin-activating enzyme (E1), a new class of potential cancer therapeutics. Cancer Res. 2007 Oct 1;67(19):9472-81.

  [2]. Kapuria V, et al. Protein cross-linking as a novel mechanism of action of a ubiquitin-activating enzyme inhibitor with anti-tumor activity. Biochem Pharmacol. 2011 Aug 15;82(4):341-9.

MSDS

Section1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE Product identifiers Product name: PYR-41 CAS-No.: 418805-02-4 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] Acute toxicity, Oral (Category 4) Skin sensitization (Category 1) Classification according to EU Directives 67/548/EEC or 1999/45/EC Harmful if swallowed. May cause sensitization by skin contact. Label elements Labelling according Regulation (EC) No 1272/2008 [CLP] Pictogram Signal wordWarning Hazard statement(s) H302Harmful if swallowed. H317May cause an allergic skin reaction. Precautionary statement(s) P280Wear protective gloves. Supplemental Hazardnone Statements According to European Directive 67/548/EEC as amended. Hazard symbol(s) R-phrase(s) R22Harmful if swallowed. R43May cause sensitization by skin contact. S-phrase(s) S36/37Wear suitable protective clothing and gloves. Other hazards - none Section3. COMPOSITION/INFORMATION ON INGREDIENTS Substances Synonyms: 4[4-(5-Nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester Formula: C17H13N3O7 Molecular Weight: 371,30 g/mol ComponentConcentration PYR-41 CAS-No.418805-02-4- 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 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 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. FIRE-FIGHTING 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) 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. Avoid breathing dust. 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. 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: -20 °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 Face shield and safety glasses 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). 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: 0,91 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 no data available 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 no data available Specific target organ toxicity - repeated exposure no data available Aspiration hazard no data available Potential health effects InhalationMay be harmful if inhaled. May cause respiratory tract irritation. IngestionHarmful if swallowed. SkinMay be harmful if absorbed through skin. May cause skin irritation. EyesMay cause 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 Section15. 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 no data available Section16. OTHER INFORMATION Further information Copyright 2011 Co. 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. Co., shall not be held liable for any damage resulting from handling or from contact with the above product. See 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-H317
• 警示性声明: P280
• 危害码 (欧洲): Xn
• 风险声明 (欧洲): 22-43
• 安全声明 (欧洲): 36/37
• 危险品运输编码: NONH for all modes of transport