127243-85-0

• 常用中文名：H-89二盐酸盐
• 常用英文名：H-89 dihydrochloride
• CAS号：127243-85-0
• 分子式：C₂₀H₂₀BrN₃O₂S
• 分子量：446.361
• 相关类别： 信号通路 自噬 自噬
• 发布时间：2018-12-30 23:35:29
• 更新时间：2024-01-03 06:35:27
• H 89是PKA高效选择性抑制剂，IC50值为48nM，对PKG、PKC、CK1、CK2等其他激酶抑制性低。

名称

• 中文名: N-[2-[P-溴苯丙烯盐基氨基]乙基]-5-异喹啉磺酰胺
• 英文名: N-[2-(p-Bromocinnamylamino)ethyl]-5-Isoquinoline Sulfonamide
• 中文别名: N-[2-[[3-(4-溴苯基)-2-丙烯-1-基]氨基]乙基]-5-异喹啉磺酰胺; H-89二盐酸盐; H-89二盐酸盐; H-89二盐酸盐
• 英文别名: N-(2-{[(2E)-3-(4-Bromophenyl)-2-propen-1-yl]amino}ethyl)-5-isoquinolinesulfonamide; MFCD00214119; 5-Isoquinolinesulfonamide, N-[2-[[(2E)-3-(4-bromophenyl)-2-propen-1-yl]amino]ethyl]-; N-(2-((3-(4-Bromophenyl)allyl)amino)ethyl)isoquinoline-5-sulfonamide dihydrochloride; N-[2-(4-bromocinnamylamino)ethyl]isoquinoline-5-sulfonamide; H-89; N-(2-{[(2E)-3-(4-bromophenyl)prop-2-en-1-yl]amino}ethyl)isoquinoline-5-sulfonamide; H 89 dihydrochloride,N-[2-[[3-(4-Bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamidedihydrochloride; H-89 dihydrochloride; H 89

物化性质

• 密度: 1.4±0.1 g/cm3
• 沸点: 639.7±65.0 °C at 760 mmHg
• 熔点: 195-200°C
• 分子式: C₂₀H₂₀BrN₃O₂S
• 分子量: 446.361
• 闪点: 340.7±34.3 °C
• 精确质量: 445.045959
• PSA: 79.47000
• LogP: 3.03
• 外观性状: 灰白色粉末
• 蒸汽压: 0.0±1.9 mmHg at 25°C
• 折射率: 1.653
• 储存条件:

  密闭于2-8 ºC阴凉干燥环境中

• 稳定性:

  遵照规定使用和储存则不会分解。

• 水溶解性: H2O: ≥10 mg/mL
• 分子结构:

  1、 摩尔折射率：113.72

  2、 摩尔体积（m³/mol）：310.7

  3、 等张比容（90.2K）：853.1

  4、 表面张力（dyne/cm）：56.8

  5、 极化率（10^-24cm³）：45.08

• 计算化学:

  1、 疏水参数计算参考值（XlogP）：3.5

  2、 氢键供体数量：2

  3、 氢键受体数量：5

  4、 可旋转化学键数量：8

  5、 拓扑分子极性表面积（TPSA）：71.1

  6、 重原子数量：27

  7、 表面电荷：0

  8、 复杂度：570

  9、 同位素原子数量：0

  10、 确定原子立构中心数量：0

  11、 不确定原子立构中心数量：0

  12、 确定化学键立构中心数量：1

  13、 不确定化学键立构中心数量：0

  14、 共价键单元数量：1

• 更多:

  1. 性状：灰白色粉末

  2. 密度（g/mL,25/4℃）：无可用

  3. 相对蒸汽密度（g/mL,空气=1）：无可用

  4. 熔点（ºC）：195-200

  5. 沸点（ºC,常压）：无可用

  6. 沸点（ºC,5.2kPa）：无可用

  7. 折射率：无可用

  8. 闪点（ºC）：无可用

  9. 比旋光度（º）：无可用

  10. 自燃点或引燃温度（ºC）：无可用

  11. 蒸气压（kPa,25ºC）：无可用

  12. 饱和蒸气压（kPa,60ºC）：无可用

  13. 燃烧热（KJ/mol）：无可用

  14. 临界温度（ºC）：无可用

  15. 临界压力（KPa）：无可用

  16. 油水（辛醇/水）分配系数的对数值：无可用

  17. 爆炸上限（%,V/V）：无可用

  18. 爆炸下限（%,V/V）：无可用

  19. 溶解性： 溶于水，>10mg/mL

生物活性

• 描述: H-89 是一种有效的 protein kinase A 抑制剂,IC50 值为 48 nM,对 PKG,PKC,Casein Kinase 和其他激酶的抑制作用很弱。
• 相关类别:
  信号通路 >> 自噬 >> 自噬
  信号通路 >> 蛋白酪氨酸激酶 >> PKA
  信号通路 >> 干细胞及 Wnt 通路 >> PKA
  研究领域 >> 其他
• 靶点:

  IC50: 48 nM (protein kinase A)

• 体外研究: H-89以与ATP竞争的方式抑制蛋白激酶A. H-89引起剂量依赖性抑制毛喉素诱导的蛋白质磷酸化,而PC12D细胞中细胞内环AMP水平没有降低。 H-89显着抑制毛喉素诱导的PC12D细胞的神经突向外生长。 H-89(30μM)抑制PC12D细胞裂解物中cAMP依赖性组蛋白IIb磷酸化活性[1]。 H-89(1-2μM)显着减慢大鼠皮肤纤维的再生速率,这很可能是由于它有害地影响T-系统潜力。 H-89(10-100μM)抑制SR对净Ca2 +的摄取,并影响大鼠皮肤纤维中收缩装置的Ca32敏感性[2]。
• 体内研究: H-89(0.2mg/100g,ip)显着增加PTZ处理的动物的癫痫发作潜伏期和阈值。 H-89(0.05,0.2 mg/100 g,ip)可预防bucladesine(300 nM)的致癫痫活性,并显着增加癫痫发作潜伏期和癫痫发作阈值[3]。
• 激酶实验: 通过测量32P从[γ-32P] ATP向底物的转移，在30℃下测定激酶活性2-5分钟。加入100μg牛血清白蛋白作为载体蛋白后，加入1mL 20％三氯乙酸终止反应。将样品以3000rpm离心10分钟，将沉淀重悬于5％三氯乙酸溶液中，将最终沉淀物溶于1mL 1N NaOH中，并在液体闪烁计数器中测量放射性。
• 细胞实验: 培养48小时后，将PCl2D细胞在含有30μMH-89的测试培养基中培养1小时，然后暴露于含有10μM毛喉素和30μMH-89的新鲜培养基中。用橡胶警察刮下细胞，并在0.5mL 6％三氯乙酸存在下超声处理。为了提取三氯乙酸，加入2mL石油醚，将制剂混合并以3000rpm离心10分钟。在吸出上层后，残留样品溶液用于测定。
• 动物实验: 获得重20-25g的雄性白化小鼠。在静脉注射前30分钟腹膜内（ip）给予己酮可可碱（25,50,100 mg / kg），布拉克丁（50,100,300 nM /小鼠）和H-89（0.05,0.1,0.2 mg / 100 g）（iv） ）输注PTZ。在组合组中，在PTZ输注前45和30分钟注射第一和第二组分。在所有组中，各个对照动物接收适当体积的载体。对于静脉输注，将针插入侧尾静脉，通过窄片胶带固定到尾静脉，并允许动物自由移动。以1mL / min的浓度速率输注PTZ溶液。
• 参考文献:

  [1]. Chijiwa T, et al. Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D

  [2]. Blazev R, et al. Effects of the PKA inhibitor H-89 on excitation-contraction coupling in skinned and intact skeletal muscle fibres. J Muscle Res Cell Motil. 2001;22(3):277-86.

  [3]. Hosseini-Zare MS, et al. Effects of pentoxifylline and H-89 on epileptogenic activity of bucladesine in pentylenetetrazol-treated mice. Eur J Pharmacol. 2011 Nov 30;670(2-3):464-70.

MSDS

Name: H-89.dihydrochloride Material Safety Data Sheet Synonym: N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide.2HCl CAS: 127243-85-0 Section 1 - Chemical Product MSDS Name:H-89.dihydrochloride Material Safety Data Sheet Synonym:N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide.2HCl Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS CAS# Chemical Name content EINECS# 127243-85-0 H-89.dihydrochloride 98 unlisted Hazard Symbols: None Listed. Risk Phrases: None Listed. Section 3 - HAZARDS IDENTIFICATION EMERGENCY OVERVIEW The toxicological properties of this material have not been fully investigated. Potential Health Effects Eye: May cause eye irritation. Skin: May cause skin irritation. Ingestion: May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated. Inhalation: May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated. Chronic: No information found. Section 4 - FIRST AID MEASURES Eyes: In case of contact, immediately flush eyes with plenty of water for at least 15 minutes. Get medical aid. Skin: In case of contact, flush skin with plenty of water. Remove contaminated clothing and shoes. Get medical aid if irritation develops and persists. Wash clothing before reuse. Ingestion: If swallowed, do not induce vomiting unless directed to do so by medical personnel. Never give anything by mouth to an unconscious person. Get medical aid. Inhalation: Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid. Notes to Physician: Treat symptomatically and supportively. Section 5 - FIRE FIGHTING MEASURES General Information: As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion. Extinguishing Media: Use water spray, dry chemical, carbon dioxide, or chemical foam. Section 6 - ACCIDENTAL RELEASE MEASURES General Information: Use proper personal protective equipment as indicated in Section 8. Spills/Leaks: Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions. Provide ventilation. Section 7 - HANDLING and STORAGE Handling: Wash thoroughly after handling. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid breathing dust, vapor, mist, or gas. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Storage: Store in a tightly closed container. Keep refrigerated. (Store below 4C/39F.) Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION Engineering Controls: Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low. Exposure Limits CAS# 127243-85-0: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166. Skin: Wear appropriate protective gloves to prevent skin exposure. Clothing: Wear appropriate protective clothing to prevent skin exposure. Respirators: Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced. Section 9 - PHYSICAL AND CHEMICAL PROPERTIES Physical State: Solid Color: white - white to off-white Odor: odorless pH: Not available. Vapor Pressure: Not available. Viscosity: Not available. Boiling Point: Not available. Freezing/Melting Point: 122-128 deg C Autoignition Temperature: Not available. Flash Point: Not available. Explosion Limits, lower: Not available. Explosion Limits, upper: Not available. Decomposition Temperature: Solubility in water: Soluble. Specific Gravity/Density: Molecular Formula: C20H20BrN3O2S.2HCl Molecular Weight: 519.0429 Section 10 - STABILITY AND REACTIVITY Chemical Stability: Not currently available. Conditions to Avoid: Dust generation. Incompatibilities with Other Materials: Strong oxidizing agents. Hazardous Decomposition Products: Carbon monoxide, oxides of nitrogen, oxides of sulfur, carbon dioxide. Hazardous Polymerization: Has not been reported Section 11 - TOXICOLOGICAL INFORMATION RTECS#: CAS# 127243-85-0 unlisted. LD50/LC50: Not available. Carcinogenicity: H-89.dihydrochloride - Not listed by ACGIH, IARC, or NTP. Section 12 - ECOLOGICAL INFORMATION Section 13 - DISPOSAL CONSIDERATIONS Dispose of in a manner consistent with federal, state, and local regulations. Section 14 - TRANSPORT INFORMATION IATA Not regulated as a hazardous material. IMO Not regulated as a hazardous material. RID/ADR Not regulated as a hazardous material. Section 15 - REGULATORY INFORMATION European/International Regulations European Labeling in Accordance with EC Directives Hazard Symbols: Not available. Risk Phrases: Safety Phrases: S 24/25 Avoid contact with skin and eyes. WGK (Water Danger/Protection) CAS# 127243-85-0: No information available. Canada None of the chemicals in this product are listed on the DSL/NDSL list. CAS# 127243-85-0 is not listed on Canada's Ingredient Disclosure List. US FEDERAL TSCA CAS# 127243-85-0 is not listed on the TSCA inventory. It is for research and development use only. SECTION 16 - ADDITIONAL INFORMATION N/A

毒性和生态

生态学数据: 该物质对环境可能有危害，对水体应给予特别注意。

安全

• 安全声明 (欧洲): S22-S24/25
• WGK德国: 3