667463-85-6

• 常用中文名：BIO-acetoxime
• 常用英文名：BIO-acetoxime
• CAS号：667463-85-6
• 分子式：C₁₈H₁₂BrN₃O₃
• 分子量：398.210
• 相关类别： 信号通路 PI3K/Akt/mTOR 信号通路 GSK-3
• 发布时间：2018-06-25 07:58:34
• 更新时间：2024-01-02 23:08:53
• BIO-acetoxime (BIA) 是一种有效、选择性的 GSK-3 抑制剂,对 GSK-3α/β 的 IC50 值均为 10 nM；BIO-acetoxime 具有抗惊厥和抗感染作用。

名称

• 中文名: 6-溴靛玉红-3'-丙酮肟
• 英文名: [[2-(6-bromo-2-oxo-1H-indol-3-ylidene)indol-3-yl]amino] acetate
• 英文别名: 2H-Indol-2-one, 3-[(3E)-3-[(acetyloxy)imino]-1,3-dihydro-2H-indol-2-ylidene]-6-bromo-1,3-dihydro-, (3Z)-; 2H-Indol-2-one, 3-[(3E)-3-[(acetyloxy)imino]-1,3-dihydro-2H-indol-2-ylidene]-6-bromo-1,3-dihydro-, (3E)-; (3Z)-3-[(3E)-3-(Acetoxyimino)-1,3-dihydro-2H-indol-2-ylidene]-6-bromo-1,3-dihydro-2H-indol-2-one; (3E)-3-[(3E)-3-(Acetoxyimino)-1,3-dihydro-2H-indol-2-ylidene]-6-bromo-1,3-dihydro-2H-indol-2-one; in1315; (3Z)-3-{(3E)-3-[(acetyloxy)imino]-1,3-dihydro-2H-indol-2-ylidene}-6-bromo-1,3-dihydro-2H-indol-2-one; 6-Bromoindirubin-3'-acetoxime; BIO-acetoxime; GSK-3 Inhibitor X

物化性质

• 密度: 1.7±0.1 g/cm3
• 分子式: C₁₈H₁₂BrN₃O₃
• 分子量: 398.210
• 精确质量: 397.006195
• PSA: 83.28000
• LogP: 2.37
• 外观性状: 粉末
• 折射率: 1.741
• 储存条件: -20℃

生物活性

• 描述: BIO-acetoxime (BIA) 是一种有效、选择性的 GSK-3 抑制剂,对 GSK-3α/β 的 IC50 值均为 10 nM；BIO-acetoxime 具有抗惊厥和抗感染作用。
• 相关类别:
  信号通路 >> PI3K/Akt/mTOR 信号通路 >> GSK-3
  信号通路 >> 干细胞及 Wnt 通路 >> GSK-3
  研究领域 >> 神经疾病
• 靶点:

  GSK-3α:10 nM (IC50)

  GSK-3β:10 nM (IC50)

  CDK5/p35:2.4 μM (IC50)

  CDK2/cyclin A:4.3 μM (IC50)

  CDK1/cyclin B:63 μM (IC50)

• 体外研究: 生物乙酰肟(BIA;化合物13)是一种有效的选择性GSK-3α/β抑制剂,IC50均为10 nM。生物乙酰肟(BIA)对CDK5/p35(IC50,2.4μM),CDK2 /细胞周期蛋白A(IC50,4.3μM)和CDK1 /细胞周期蛋白B(IC50,63μM)的作用较弱[1]。生物乙酰肟(BIA)(5μM和10μM)增加了HSV-1感染细胞的活力,但对模拟细胞的形态和活力几乎没有影响。此外,BIO-乙酰肟(BIA)(0.625,1.25,2.5,5和10μM)显着降低OC3细胞中HSV-1颗粒的释放,EC50为0.68±0.28μM。生物乙酰肟(BIA)抑制HSV-1基因的表达,并且可能不影响HSV-1衣壳的核靶向。此外,延迟添加BIO-乙酰肟(BIA)也可抑制HSV-1感染[2]。
• 体内研究: BIO-乙酰肟(BIA)显示在0.5mg/kg的局灶性毛果芸香碱大鼠模型中的抗惊厥作用,以及在0.5,2.5和5mg/kg的6-Hz完全点燃的FVB/N小鼠中通过ip施用[3]。
• 细胞实验: 将OC3细胞接种在3.5和6cm直径的培养皿中，分别用于蛋白质印迹分析和RNA分离。除非另有说明，否则细胞以5的感染复数（moi）进行模拟处理或暴露于HSV-1。首先将糖原合成酶激酶-3（GSK-3）抑制剂BIO-乙酰肟（BIA）溶解在DMSO中以制备储备溶液。含有DMSO的培养基用作溶剂对照。在模拟或HSV-1感染之前，将细胞仅用培养基，含有0.1％DMSO或BIO-乙酰肟（BIA）的培养基预处理45分钟。在整个感染期间也存在生物乙酰肟（BIA）。为了检查对病毒的直接影响，在室温下用含有5μMBIO-乙酰肟（BIA）的培养基直接处理HSV-1 1小时。用倒置显微镜观察细胞形态[2]。
• 动物实验: 小鼠[3]雄性FVB / N小鼠用于测试BIO-乙酰肟在完全点燃的小鼠中的抗惊厥作用。为了实现完全点燃状态，除了周末之外，每天两次以固定的惊厥阈值电流刺激小鼠，刺激之间的最小间隔为4小时。然后每周刺激点燃的小鼠仅2天，每天两次以维持完全点燃的状态。同时，未经训练的小鼠保持原始刺激方案最多1-2周。通过在周一早晨刺激这些动物，在“癫痫”完全点燃的小鼠中研究了BIO-乙酰肟（BIA）的抗惊厥作用。在星期一下午，在刺激前30分钟向动物腹膜内（ip）注射载体。星期二早上，老鼠再次受到刺激。周二下午，小鼠腹腔注射BIO-乙酰肟（BIA），30分钟后刺激。使用Racine量表评估癫痫发作的严重程度。将治疗前评分与周二治疗后获得的治疗后评分进行比较。为了确认任何观察到的效果，重复实验，尊重1周的冲洗。在该清洗周期间，所有小鼠被刺激2天（每天两次）以维持点燃状态。到目前为止，长时间的复合测试尚未得到验证。这意味着在一批点燃的小鼠中只能测试一剂BIO-乙酰肟[3]。
• 参考文献:

  [1]. Meijer L, et al. GSK-3-selective inhibitors derived from Tyrian purple indirubins. Chem Biol. 2003 Dec;10(12):1255-66.

  [2]. BIO-acetoxime, et al. Antiherpetic potential of 6-bromoindirubin-3'-acetoxime (BIO-acetoxime) in human oral epithelial cells. Arch Virol. 2013 Jun;158(6):1287-96.

  [3]. BIO-acetoxime, et al. Identification of GSK-3 as a Potential Therapeutic Entry Point for Epilepsy. ACS Chem Neurosci. 2018 Nov 6.

MSDS

SECTION 1: Identification of the substance/mixture and of the company/undertaking Product identifiers Product name: BIO-Acetoxime 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.: 667463-85-6 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 Acute aquatic toxicity (Category 1), H400 Chronic aquatic toxicity (Category 1), H410 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 N, Xn Dangerous for theR22, R50/53 environment, Harmful 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. H410Very toxic to aquatic life with long lasting effects. Precautionary statement(s) P273Avoid release to the environment. P501Dispose of contents/ container to an approved waste disposal plant. Supplemental Hazardnone Statements Other hazards - none SECTION 3: Composition/information on ingredients Substances Synonyms: BIA (2'Z,3'E)-6-Bromoindirubin-3'-acetoxime 6-Bromoindirubin-3'-acetoxime 6-Bromoindirubin acetoxime (3Z)-3-[(3E)-3-[(Acetyloxy)imino]-1,3-dihydro-2H-indol-2-ylidene]-6- bromo-1,3-dihydro-2H-Indol-2-one Formula: C18H12BrN3O3 Molecular Weight: 398,21 g/mol CAS-No.: 667463-85-6 Hazardous ingredients according to Regulation (EC) No 1272/2008 ComponentClassificationConcentration (2'Z,3'E)-6-Bromoindirubin-3'-acetoxime Acute Tox. 4; Aquatic Acute 1; - Aquatic Chronic 1; H302, H410 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 Carbon oxides, nitrogen oxides (NOx), Hydrogen bromide gas Advice for firefighters Wear self contained breathing apparatus for fire fighting 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 vapors, mist or gas. Ensure adequate ventilation. Avoid breathing dust. For personal protection see section 8. 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. 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 Specific end use(s) A part 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 Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the environment must be avoided. 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 pointnot applicable 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: 4,635 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 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 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 PBT/vPvB assessment not available as chemical safety assessment not required/not conducted Other adverse effects Very toxic to aquatic life with long lasting 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: 3077IMDG: 3077IATA: 3077 UN proper shipping name ADR/RID: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. ( (2'Z,3'E)-6- Bromoindirubin-3'-acetoxime) IMDG: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. ( (2'Z,3'E)-6- Bromoindirubin-3'-acetoxime) IATA:Environmentally hazardous substance, solid, n.o.s. ( (2'Z,3'E)-6-Bromoindirubin-3'-acetoxime) Transport hazard class(es) ADR/RID: 9IMDG: 9IATA: 9 Packaging group ADR/RID: IIIIMDG: IIIIATA: III Environmental hazards ADR/RID: yesIMDG Marine Pollutant: yesIATA: yes Special precautions for user Further information EHS-Mark required (ADR 2.2.9.1.10, IMDG code 2.10.3) for single packagings and combination packagings containing inner packagings with Dangerous Goods > 5L for liquids or > 5kg for solids. SECTION 15 - REGULATORY INFORMATION N/A SECTION 16 - ADDITIONAL INFORMATION N/A

安全

• 符号: GHS07, GHS09
• 信号词: Warning
• 危害声明: H302-H410
• 警示性声明: P273-P501
• 危害码 (欧洲): N
• 危险品运输编码: UN 3077 9 / PGIII