420831-40-9

• 常用中文名：N-(3-溴苯基)-3-[(六氢-1H-氮杂卓-1-基)磺酰基]-苯甲酰胺
• 常用英文名：AK-7
• CAS号：420831-40-9
• 分子式：C₁₉H₂₁BrN₂O₃S
• 分子量：437.351
• 相关类别： 信号通路 细胞周期/DNA损伤 抗衰老酶
• 发布时间：2018-12-14 00:30:25
• 更新时间：2024-01-02 19:19:26
• AK-7 是一种可透过细胞及血脑屏障的 SIRT2 抑制剂，IC₅₀ 值为 15.5 μM。

名称

• 中文名: N-(3-溴苯基)-3-[(六氢-1H-氮杂卓-1-基)磺酰基]-苯甲酰胺
• 英文名: 3-(azepan-1-ylsulfonyl)-N-(3-bromophenyl)benzamide
• 英文别名: unii-308b6b695n; 3-(1-Azepanylsulfonyl)-N-(3-bromophenyl)benzamide; Benzamide, N-(3-bromophenyl)-3-[(hexahydro-1H-azepin-1-yl)sulfonyl]-; SIRT2 Inhibitor II; AK-7

物化性质

• 密度: 1.5±0.1 g/cm3
• 分子式: C₁₉H₂₁BrN₂O₃S
• 分子量: 437.351
• 精确质量: 436.045624
• PSA: 74.86000
• LogP: 4.93
• 折射率: 1.631
• 储存条件: 2-8℃

生物活性

• 描述: AK-7 是一种可透过细胞及血脑屏障的 SIRT2 抑制剂,IC50 值为 15.5 μM。
• 相关类别:
  信号通路 >> 细胞周期/DNA损伤 >> 抗衰老酶
  信号通路 >> 表观遗传学 >> 抗衰老酶
  研究领域 >> 神经疾病
• 靶点:

  SIRT2:15.5 μM (IC50)

• 体外研究: AK-7(10μM)降低来自野生型小鼠的幼稚N2a神经母细胞瘤细胞和海马切片培养物中的胆固醇水平。 AK-7(1μM)显示AK-7在纹状体亨廷顿氏病(HD)神经元中的神经保护作用[1]。 AK-7(12.5μM)降低了初级中脑培养物中DA神经元的比例[3]。
• 体内研究: AK-7(15 mg/kg /剂量,ip)在野生型和HD小鼠中具有脑透性[1]。 AK-7(10,20mg/kg,ip)改善行为和神经病理学表型并延长R6/2HD小鼠的存活。 AK-7(20mg/kg)改善R6/2小鼠的HD神经病理学。 AK-7还可以减少R6/2脑中的聚谷氨酰胺聚集。此外,AK-7处理的140CAG小鼠显示与未处理的野生型小鼠平行的运动表现变化,20mg/kg剂量最有效并且与未处理的140CAG小鼠显着不同[2]。
• 细胞实验: 神经元核抗原（NeuN）阳性神经元和一些星形胶质细胞来源于E16大鼠胚胎的机械解离的神经节隆起。 HD模型基于突变亨廷顿蛋白的表达。除非另有说明，否则用AK-7处理的培养物在10μM下持续24小时。包含与对照相同浓度的DMSO。低剂量，AK-7的慢性治疗被引入DIV4的神经元，并且每周继续与正常的培养基改变一致[1]。
• 动物实验: 在25％Cremophor EL（BASF）/ 10％DMSO水溶液中以1.5mg / mL溶解的AK-7通过腹膜内注射施用于15mg / kg /剂量的11周龄小鼠，以及血清和脑中的化合物水平。在牺牲后测量。收集血液并以7,000rpm离心7分钟，然后吸出血清并立即在液氮中冷冻。将脑迅速冷冻在液氮中并储存在-80℃。将脑称重，然后使用Polytron匀浆器在4体积的10％Cremophor RH40水溶液中均化，并将2％v / v磷酸加入到匀浆中，涡旋，并在10,000g，25℃下离心1小时。吸出上清液，立即进行固相萃取。将血清样品涡旋至2％v / v磷酸中，并以2500rpm离心10分钟[1]。
• 参考文献:

  [1]. Taylor DM, et al. A brain-permeable small molecule reduces neuronal cholesterol by inhibiting activity of sirtuin 2 deacetylase. ACS Chem Biol. 2011 Jun 17;6(6):540-6.

  [2]. Chopra V, et al. The sirtuin 2 inhibitor AK-7 is neuroprotective in Huntington's disease mouse models. Cell Rep. 2012 Dec 27;2(6):1492-7.

  [3]. Szego EM, et al. Sirtuin 2 enhances dopaminergic differentiation via the AKT/GSK-3β/β-catenin pathway. Neurobiol Aging. 2017 Aug;56:7-16.

MSDS

Section1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE Product identifiers Product name: AK-7 CAS-No.: 420831-40-9 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] Eye irritation (Category 2) Classification according to EU Directives 67/548/EEC or 1999/45/EC Irritating to eyes. Label elements Labelling according Regulation (EC) No 1272/2008 [CLP] Pictogram Signal wordWarning Hazard statement(s) H319Causes serious eye irritation. Precautionary statement(s) 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) R36Irritating to eyes. S-phrase(s) S26In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. Other hazards - none Section3. COMPOSITION/INFORMATION ON INGREDIENTS Substances Synonyms: N-(3-Bromophenyl)-3-[(hexahydro-1H-azepin-1-yl)sulfonyl]-benzamide Formula: C19H21BrN2O3S Molecular Weight: 437,35 g/mol ComponentConcentration N-(3-Bromophenyl)-3-[(hexahydro-1H-azepin-1-yl)sulfonyl]-benzamide CAS-No.420831-40-9- 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 bromide gas 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: 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: 3,886 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 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. IngestionMay be harmful if swallowed. SkinMay be harmful if absorbed through skin. May cause 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: H319
• 警示性声明: P305 + P351 + P338
• 危险品运输编码: NONH for all modes of transport
• 海关编码: 2933990090

海关

海关编码	2933990090
中文概述	2933990090. 其他仅含氮杂原子的杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%
申报要素	品名, 成分含量, 用途, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期
Summary	2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%