6151-30-0

• 常用中文名：米帕林盐酸盐
• 常用英文名：Quinacrine Dihydrochloride Dihydrate
• CAS号：6151-30-0
• 分子式：C₂₃H₃₆Cl₃N₃O₃
• 分子量：508.909
• 相关类别： 原料药 抗寄生虫病药 抗疟药
• 发布时间：2018-03-23 08:00:00
• 更新时间：2024-01-02 13:28:56
• Quinacrine hydrochloride hydrate (Mepacrine hydrochloride hydrate) 是一种抗疟剂 (antimalarial),在体内外均具有抗肿瘤作用。Quinacrine hydrochloride hydrate 抑制 NF-κB 并激活 p53 信号转导,诱导肿瘤细胞发生凋亡 (apoptosis)。

名称

• 中文名: 米帕林盐酸盐
• 英文名: Mepacrine hydrochloride
• 中文别名: N4-(6-氯-2-甲氧基-9-吖啶基)-N1,N1-二乙基-1,4-戊二胺二盐酸盐二水合物; 奎纳克林盐酸盐
• 英文别名: Atebrin hydrochloride; Quinacrinehydrochlorid; MFCD00150069; 866 R.P.; Chemiochin; Acrichine; mepacrinehydrochloridedihydrate; atabrinehydrochloridedihydrate; QuinacrineHCl; QUINACRINE,ATABRINE MEPACNINE; Mepacrine dihydrochloride; Chinacrin hydrochloride; hloride2h2-o; ochloride,dihydrate; Mecryl; Erion; Pentilen; mepacrinehcl; N-(6-Chloro-2-methoxy-9-acridinyl)-N,N-diethyl-1,4-pentanediamine dihydrochloride dihydrate; AtabrineMepacnine; QUINACRINE DIHYDROCHLORIDE; Palusan; 1,4-Pentanediamine, N-(6-chloro-2-methoxy-9-acridinyl)-N,N-diethyl-, hydrochloride, hydrate (1:2:2); Crinodora; Akrichin; Italchin; Metochin; Metoquine; Palacrin; 69-05-6 {Anhydrous}; Acriquine; Malaricida

物化性质

• 沸点: 557.1ºC at 760 mmHg
• 熔点: 247 °C
• 分子式: C₂₃H₃₆Cl₃N₃O₃
• 分子量: 508.909
• 精确质量: 507.182220
• PSA: 55.85000
• LogP: 7.52080
• 外观性状: 粉末
• 储存条件:

  密封储存，储存于阴凉、干燥的库房。

• 稳定性: 常温常压下稳定， 对光照敏感。吸收湿空气和空气中的水分。 避免与不相容材料，光照，湿空气，水接触。 与湿空气，水，强酸反应。
• 水溶解性: 2.8 g/100 mL
• 计算化学:

  1、 疏水参数计算参考值（XlogP）：6.2

  2、 氢键供体数量：3

  3、 氢键受体数量：2

  4、 可旋转化学键数量：9

  5、 互变异构体数量：2

  6、 拓扑分子极性表面积（TPSA）：39.8

  7、 重原子数量：28

  8、 表面电荷：2

  9、 复杂度：461

  10、 同位素原子数量：0

  11、 确定原子立构中心数量：1

  12、 不确定原子立构中心数量：0

  13、 确定化学键立构中心数量：0

  14、 不确定化学键立构中心数量：0

  15、 共价键单元数量：1

• 更多:

  1. 性状：黄色粉末

  2. 密度（g/mL,25℃）：未确定

  3. 相对蒸汽密度（g/mL,空气=1）：未确定

  4. 熔点（ºC）：247

  5. 沸点（ºC,常压）：未确定

  6. 沸点（ºC，39mmHg）：未确定

  7. 折射率(n20/D)：未确定

  8. 闪点（ºF）：未确定

  9. 比旋光度（º）：未确定

  10. 自燃点或引燃温度（ºC）：未确定

  11. 蒸气压（mmHg,20ºC）：未确定

  12. 饱和蒸气压（kPa,25ºC）：未确定

  13. 燃烧热（KJ/mol）：未确定

  14. 临界温度（ºC）：未确定

  15. 临界压力（KPa）：未确定

  16. 油水（辛醇/水）分配系数的对数值：未确定

  17. 爆炸上限（%,V/V）：未确定

  18. 爆炸下限（%,V/V）：未确定

  19. 溶解性：溶于水

生物活性

• 描述: Quinacrine hydrochloride hydrate (Mepacrine hydrochloride hydrate) 是一种抗疟剂 (antimalarial),在体内外均具有抗肿瘤作用。Quinacrine hydrochloride hydrate 抑制 NF-κB 并激活 p53 信号转导,诱导肿瘤细胞发生凋亡 (apoptosis)。
• 相关类别:
  信号通路 >> 细胞凋亡 >> 细胞凋亡
  研究领域 >> 癌症
  研究领域 >> 感染
  信号通路 >> 自噬 >> 自噬
  信号通路 >> 自噬 >> 自噬
• 体外研究: 奎纳克林(5-20μM；24小时)抑制SGC-7901细胞的生长[1]。奎纳克林(7.5和15μM；24小时)诱导SGC-7901细胞凋亡,凋亡与线粒体依赖性信号通路有关,涉及p53上调和caspase-3激活途径[1]。奎纳克林(15μM；24小时)治疗显著提高促凋亡蛋白水平,包括细胞色素c、Bax和p53,并降低抗凋亡蛋白Bcl-2的水平,从而改变Bax/Bcl-2的比例,有利于细胞凋亡[1]。细胞活力测定[1]细胞系：SGC-7901细胞浓度：0、5、10、15、20μM孵育时间：24小时结果：细胞活力呈剂量依赖性抑制,IC50平均值为16.18μM。细胞凋亡分析[1]细胞系：SGC-7901细胞浓度：7.5和15μM孵育时间：24小时结果：细胞百分比凋亡细胞(包括早期和晚期凋亡)增加到26.30%,而对照组为3.37%。westernblot分析[1]细胞系：SGC-7901细胞浓度：15μM孵育时间：24h结果：细胞色素c蛋白相对数量上调,由0.10增加到0.24。p53蛋白的相对数量显著增加,从0.06增加到0.19。Bax/Bcl-2比值由1.21显著升高至2.59。
• 体内研究: 奎纳克林(100mg/kg,每周三次,连续两周)在第30/31天显著抑制循环的原代细胞,并增加中位生存时间(MST)。奎纳克林在试验剂量下不会降低治疗动物的体重[2]。动物模型：雌性SCID小鼠急性髓系白血病(AML)-PS模型[2]剂量：100mg/kg给药：口服灌胃给药(po)；每周三次,连续两周。结果：在第一次AML小鼠体内研究中,评估第天血液样本中检测到的循环白血病细胞(白细胞百分比(WBC))30/31在对照组小鼠中显示72%的人类肿瘤细胞,而在奎纳克林治疗的小鼠中,这一比例仅为2.2%。对照组小鼠的MST为34天,而奎纳克林组小鼠的MST为46天。
• 参考文献:

  [1]. Xiaoyang Wu, et al. Quinacrine Inhibits Cell Growth and Induces Apoptosis in Human Gastric Cancer Cell Line SGC-7901. Curr Ther Res Clin Exp. 2012 Feb;73(1-2):52-64.

  [2]. Anna Eriksson, et al. Towards repositioning of quinacrine for treatment of acute myeloid leukemia - Promising synergies and in vivo effects. Leuk Res. 2017 Dec;63:41-46.

MSDS

Section 1. Chemical Product and Company Identification Quinacrine hydrochloride dihydrateCatalog Common Name/ Number(s). Trade Name CAS#6151-30-0 Manufacturer RTECSAR7876000 SPECTRUM CHEMICAL MFG. CORP. TSCATSCA 8(b) inventory: Quinacrine hydrochloride dihydrate Commercial Name(s)Not available. CI#Not available. Synonym6-Chloro-9=[[44-(diethylamino-1-methylbutyl]amino]-2-methoxyacridine IN CASE OF EMERGENCY hydrochloride Chemical NameNot available. Not available.CALL (310) 516-8000 Chemical Family Chemical FormulaC23H30ClN3O.2HCl.2H2O SPECTRUM CHEMICAL MFG. CORP. Section 2.Composition and Information on Ingredients Exposure Limits TWA (mg/m3)STEL (mg/m3) CEIL (mg/m3) NameCAS #% by Weight 1) Quinacrine hydrochloride dihydrate6151-30-0100 Toxicological DataQuinacrine hydrochloride dihydrate: on IngredientsORAL (LD50):Acute: 660 mg/kg [Rat]. 433 mg/kg [Rabbit]. Section 3. Hazards Identification Potential Acute Health Effects Very hazardous in case of ingestion. Hazardous in case of skin contact (irritant), of eye contact (irritant), of inhalation. Slightly hazardous in case of skin contact (permeator). Potential Chronic HealthCARCINOGENIC EFFECTS: Not available. EffectsMUTAGENIC EFFECTS: Not available. TERATOGENIC EFFECTS: Not available. DEVELOPMENTAL TOXICITY: PROVEN The substance is toxic to blood, the nervous system, the reproductive system, liver, heart. Repeated or prolonged exposure to the substance can produce target organs damage. Quinacrine hydrochloride dihydrate Section 4. First Aid Measures Eye ContactCheck for and remove any contact lenses. Immediately flush eyes with running water for at least 15 minutes, keeping eyelids open. Cold water may be used. Do not use an eye ointment. Seek medical attention. Skin ContactAfter contact with skin, wash immediately with plenty of water. Gently and thoroughly wash the contaminated skin with running water and non-abrasive soap. Be particularly careful to clean folds, crevices, creases and groin. Cold water may be used. Cover the irritated skin with an emollient. If irritation persists, seek medical attention. Wash contaminated clothing before reusing. Serious Skin ContactWash with a disinfectant soap and cover the contaminated skin with an anti-bacterial cream. Seek immediate medical attention. InhalationAllow the victim to rest in a well ventilated area. Seek immediate medical attention. Serious InhalationNot available. IngestionDo not induce vomiting. Examine the lips and mouth to ascertain whether the tissues are damaged, a possible indication that the toxic material was ingested; the absence of such signs, however, is not conclusive. Loosen tight clothing such as a collar, tie, belt or waistband. If the victim is not breathing, perform mouth-to-mouth resuscitation. Seek immediate medical attention. Serious IngestionNot available. Section 5. Fire and Explosion Data Flammability of the Product May be combustible at high temperature. Auto-Ignition Temperature Not available. Flash PointsNot available. Flammable LimitsNot available. Products of CombustionThese products are carbon oxides (CO, CO2), nitrogen oxides (NO, NO2...), halogenated compounds. Fire Hazards in Presence of Not available. Various Substances Explosion Hazards in Presence Risks of explosion of the product in presence of mechanical impact: Not available. of Various SubstancesRisks of explosion of the product in presence of static discharge: Not available. Fire Fighting MediaSMALL FIRE: Use DRY chemical powder. and InstructionsLARGE FIRE: Use water spray, fog or foam. Do not use water jet. Special Remarks onNot available. Fire Hazards Special Remarks on Explosion Not available. Hazards Section 6. Accidental Release Measures Small SpillUse appropriate tools to put the spilled solid in a convenient waste disposal container. Finish cleaning by spreading water on the contaminated surface and dispose of according to local and regional authority requirements. Large SpillUse a shovel to put the material into a convenient waste disposal container. Finish cleaning by spreading water on the contaminated surface and allow to evacuate through the sanitary system. Quinacrine hydrochloride dihydrate Section 7. Handling and Storage PrecautionsKeep away from heat. Keep away from sources of ignition. Empty containers pose a fire risk, evaporate the residue under a fume hood. Ground all equipment containing material. Do not ingest. Do not breathe dust. Wear suitable protective clothing In case of insufficient ventilation, wear suitable respiratory equipment If ingested, seek medical advice immediately and show the container or the label. Avoid contact with skin and eyes StorageKeep container dry. Keep in a cool place. Ground all equipment containing material. Keep container tightly closed. Keep in a cool, well-ventilated place. Combustible materials should be stored away from extreme heat and away from strong oxidizing agents. Section 8. Exposure Controls/Personal Protection Engineering ControlsUse process enclosures, local exhaust ventilation, or other engineering controls to keep airborne levels below recommended exposure limits. If user operations generate dust, fume or mist, use ventilation to keep exposure to airborne contaminants below the exposure limit. Personal ProtectionSplash goggles. Lab coat. Dust respirator. Be sure to use an approved/certified respirator or equivalent. Gloves. Personal Protection in Case of Splash goggles. Full suit. Dust respirator. Boots. Gloves. A self contained breathing apparatus should be used a Large Spillto avoid inhalation of the product. Suggested protective clothing might not be sufficient; consult a specialist BEFORE handling this product. Exposure LimitsNot available. Section 9. Physical and Chemical Properties Physical state and appearance Solid.OdorNot available. TasteNot available. 508.91 g/mole Molecular Weight ColorYellow. pH (1% soln/water)Not available. Boiling PointNot available. Melting PointDecomposes. Critical TemperatureNot available. Specific GravityNot available. Not applicable. Vapor Pressure Vapor DensityNot available. VolatilityNot available. Odor ThresholdNot available. Water/Oil Dist. Coeff.Not available. Not available. Ionicity (in Water) Dispersion PropertiesSee solubility in water. Soluble in cold water. Solubility Section 10. Stability and Reactivity Data The product is stable. Stability Instability TemperatureNot available. Not available. Conditions of Instability Incompatibility with various Not available. substances Quinacrine hydrochloride dihydrate CorrosivityNon-corrosive in presence of glass. Special Remarks onNot available. Reactivity Special Remarks onNot available. Corrosivity PolymerizationNo. Section 11. Toxicological Information Routes of EntryEye contact. Inhalation. Ingestion. Toxicity to AnimalsAcute oral toxicity (LD50): 433 mg/kg [Rabbit]. Chronic Effects on HumansDEVELOPMENTAL TOXICITY: PROVEN The substance is toxic to blood, the nervous system, the reproductive system, liver, heart. Other Toxic Effects onVery hazardous in case of ingestion. HumansHazardous in case of skin contact (irritant), of inhalation. Slightly hazardous in case of skin contact (permeator). Special Remarks onNot available. Toxicity to Animals Special Remarks onNot available. Chronic Effects on Humans Special Remarks on otherNot available. Toxic Effects on Humans Section 12. Ecological Information Not available. Ecotoxicity Not available. BOD5 and COD Products of BiodegradationPossibly hazardous short term degradation products are not likely. However, long term degradation products may arise. Toxicity of the ProductsThe products of degradation are more toxic. of Biodegradation Not available. Special Remarks on the Products of Biodegradation Section 13. Disposal Considerations Waste Disposal Section 14. Transport Information DOT ClassificationNot a DOT controlled material (United States). Not applicable. Identification Special Provisions forNot applicable. Transport Quinacrine hydrochloride dihydrate DOT (Pictograms) Section 15. Other Regulatory Information and Pictograms TSCA 8(b) inventory: Quinacrine hydrochloride dihydrate Federal and State Regulations California Proposition 65 Warnings Other RegulationsOSHA: Hazardous by definition of Hazard Communication Standard (29 CFR 1910.1200). CLASS D-1B: Material causing immediate and serious toxic effects (TOXIC). Other ClassificationsWHMIS (Canada) CLASS D-2A: Material causing other toxic effects (VERY TOXIC). DSCL (EEC)R36/38- Irritating to eyes and skin. R48/22- Harmful: danger of serious damage to health by prolonged exposure if swallowed. Health Hazard HMIS (U.S.A.)2 National Fire Protection 1 Flammability 1 Association (U.S.A.) Fire Hazard 2 0 Reactivity Health Reactivity 0 Specific hazard Personal Protection E WHMIS (Canada) (Pictograms) DSCL (Europe) (Pictograms) TDG (Canada) (Pictograms) ADR (Europe) (Pictograms) Protective Equipment Gloves. Lab coat. Quinacrine hydrochloride dihydrate Dust respirator. Be sure to use an approved/certified respirator or equivalent. Wear appropriate respirator when ventilation is inadequate. SECTION 16 - ADDITIONAL INFORMATION N/A

毒性和生态

毒理学数据: 1、急性毒性：小鼠经静脉LDLo：37mg/kg； 2、生殖毒性 大鼠经睾丸TDLo：4mg/kg； 生态学数据: 对水是极其危害的，即使是小量，对水体中的鱼和浮游生物是有毒害的。 若无政府许可，勿将材料排入周围环境。 CHEMICAL IDENTIFICATION RTECS NUMBER : AR7876000 CHEMICAL NAME : Acridine, 6-chloro-9-((4-(diethylamino)-1-methylbutyl)amino)-2- methoxy-, dihydrochloride, dihydrate CAS REGISTRY NUMBER : 6151-30-0 LAST UPDATED : 199112 DATA ITEMS CITED : 2 MOLECULAR FORMULA : C23-H30-Cl-N3-O.2Cl-H.2H2-O MOLECULAR WEIGHT : 507.96 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 37 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold REFERENCE : TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 44,225,1978 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intratesticular DOSE : 4 mg/kg SEX/DURATION : male 1 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct REFERENCE : CCPTAY Contraception. (Geron-X, Inc., POB 1108, Los Altos, CA 94022) V.1- 1970- Volume(issue)/page/year: 6,329,1972

安全

• 危害码 (欧洲): Xn: Harmful;
• 风险声明 (欧洲): R22;R36/37/38
• 安全声明 (欧洲): S26-S37/39