| 中文名 | 丝裂霉素 |
|---|---|
| 英文名 | mitomycin C |
| 中文别名 |
自力霉素
自力霉素,嘧吡霉素 密吐霉素 丝裂霉素c |
| 英文别名 |
MFCD00078109
Mitomycin C(Ametycine) EINECS 200-008-6 |
| 描述 | Mitomycin C是一种抗肿瘤药物和抗生素,可有效的抑制DNA合成 (DNA synthesis)。 |
|---|---|
| 相关类别 | |
| 靶点 |
DNA synthesis[1] |
| 体外研究 | HCT116(p53 -/-)细胞对丝裂霉素C或单独的TRAIL最不敏感。然而,令人惊讶的是,用MMC和TRAIL的组合处理显着降低了细胞活力。尽管单独的丝裂霉素C和TRAIL是中等有效的,但丝裂霉素C显着增强TRAIL对抑制细胞增殖的作用。单独的丝裂霉素C和TRAIL处理分别诱导9.5％和35.0％的细胞凋亡。然而,用丝裂霉素C和TRAIL联合治疗可使细胞凋亡增加至66.6％[1]。丝裂霉素C是一种细胞毒性化学治疗剂,以DNA交联形式引起DNA损伤以及各种DNA单加合物,已知可诱导p53 [2]。 |
| 体内研究 | 每隔一天用丝裂霉素C(ip,1mg/kg)和TRAIL(iv,100μg)处理携带异种移植的HCT116(p53 -/-)结肠肿瘤和HT-29结肠肿瘤的小鼠。用联合治疗方案的10个连续周期治疗动物。联合疗法显着抑制肿瘤生长,并且不影响小鼠的体重,表明丝裂霉素C和TRAIL的治疗组合具有良好的耐受性并且在体内具有抗肿瘤活性[1]。膀胱内丝裂霉素C滴注对体重有影响,这在正常,NaCl滴注或表阿霉素滴注的大鼠中未观察到。连续3次每周滴注1mg/mL丝裂霉素C几乎没有体重增加,而其他3组中的大鼠与MMC治疗的大鼠相比具有统计学上显着的体重增加[3]。 |
| 细胞实验 | 使用结肠腺癌HCT116和HT-29人结肠癌细胞。 CellTiter-Glo发光细胞存活率测定用于测量细胞活力，其使用独特，稳定形式的荧光素酶来测量ATP作为活细胞的指示物，并且产生的发光信号与培养物中存在的活细胞数成比例。 。将细胞用丝裂霉素C（5μM）预处理12小时或24小时，然后暴露于不同浓度的TRAIL 12小时。加入等体积（100μL）的CellTiter-GloTM试剂，将溶液在轨道振荡器上轻轻混合2分钟。将混合物在室温下孵育10分钟以使发光信号稳定，然后使用Xenogen IVIS系统进行成像以定量细胞活力[1]。 |
| 动物实验 | 小鼠[1]通过腹膜内注射用丝裂霉素C（1mg / kg）处理4至6周龄的NCr裸小鼠24小时，然后静脉内施用一剂纯化的rhTRAIL（100μg）。作为阴性对照，以相同的治疗频率用盐水（载体）注射（ip和iv）小鼠的子集。动物连续治疗3周。使用肿瘤体积的卡尺测量每周监测肿瘤大小。大鼠[3]年龄为13周的年轻成年雌性Wistar大鼠，中位体重为217 g（范围187至255），随机分为4组，每组10只，即没有滴注的正常组，0.9％NaCl或安慰剂组接受滴注化学治疗剂，丝裂霉素C（1mg / mL）组和表柔比星（1mg / mL）组的溶剂。 |
| 参考文献 |
| 密度 | 1.9±0.1 g/cm3 |
|---|---|
| 沸点 | 532.0±60.0 °C at 760 mmHg |
| 熔点 | 360 °C |
| 分子式 | C15H18N4O5 |
| 分子量 | 334.327 |
| 闪点 | 275.5±32.9 °C |
| 精确质量 | 334.127716 |
| PSA | 146.89000 |
| LogP | -0.27 |
| 外观性状 | 暗蓝色灰色结晶粉末 |
| 蒸汽压 | 0.0±3.2 mmHg at 25°C |
| 折射率 | 1.828 |
| 储存条件 | 本品密封阴凉避光保存。 |
| 稳定性 | Stable. Incompatible with strong acids, strong bases, strong oxidizing agents. |
| 水溶解性 | soluble |
| 分子结构 | 1、 摩尔折射率：80.79 2、 摩尔体积（cm3/mol）：213.6 3、 等张比容（90.2K）：633.5 4、 表面张力（dyne/cm）：77.2 5、 极化率（10-24cm3）：32.02 |
| 计算化学 | 1、 疏水参数计算参考值（XlogP）：-0.4 2、 氢键供体数量：3 3、 氢键受体数量：8 4、 可旋转化学键数量：4 5、 互变异构体数量：42 6、 拓扑分子极性表面积（TPSA）：147 7、 重原子数量：24 8、 表面电荷：0 9、 复杂度：757 10、同位素原子数量：0 11、确定原子立构中心数量：4 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：蓝紫色有光泽结晶或结晶性粉末，无臭。固体稳定，但在酸性和碱性溶液中易失活 2. 密度（g/mL,25/4℃）：不确定 3. 相对蒸汽密度（g/mL,空气=1）：不确定 4. 熔点（ºC）：>360 5. 沸点（ºC,常压）：不确定 6. 沸点（ºC, 5.2 kPa）：不确定 7. 折射率：不确定 8. 闪点（ºC）：不确定 9. 比旋光度（º）：不确定 10. 自燃点或引燃温度（ºC）：不确定 11. 蒸气压（kPa,25 ºC）：不确定 12. 饱和蒸气压（kPa,60 ºC）：不确定 13. 燃烧热（KJ/mol）：不确定 14. 临界温度（ºC）：不确定 15. 临界压力（KPa）：不确定 16. 油水（辛醇/水）分配系数的对数值：不确定 17. 爆炸上限（%,V/V）：不确定 18. 爆炸下限（%,V/V）：不确定 19. 溶解性：本品溶于水(H2O: 4mL/vial Stock solutions should be filter sterilized and stored at 2-8 °C in the dark., clear to slightly hazy, blue to purple)、甲醇、丙酮和乙酸乙酯等有机溶剂，微溶于苯、乙醚和四氯化碳，不溶于石油醚 |
Synonym:Ametycine Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS
Risk Phrases: 25 33 Section 3 - HAZARDS IDENTIFICATION EMERGENCY OVERVIEW
Toxic if swallowed. Danger of cumulative effects. Potential Health Effects Eye: May cause eye irritation. Skin: May cause skin irritation. Ingestion: Harmful if swallowed. May cause liver damage. May cause digestive tract disturbances. May cause bone marrow depression. Inhalation: May cause respiratory tract irritation. May cause effects similar to those described for ingestion. May cause pulmonary fibrosis and permanent damage. Chronic: May cause cancer according to animal studies. Chronic exposure may cause liver damage. Adverse reproductive effects have been reported in animals. Potential cancer hazard. Section 4 - FIRST AID MEASURES Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid. Skin: Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse. Ingestion: Do not induce vomiting. If victim is conscious and alert, give 2-4 cupfuls of milk or water. 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. Do NOT use mouth-to-mouth resuscitation. Notes to Physician: 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. Non-combustible, substance itself does not burn but may decompose upon heating to produce irritating, corrosive and/or toxic fumes. Extinguishing Media: In case of fire, use water, dry chemical, chemical foam, or alcohol-resistant foam. Substance is noncombustible; use agent most appropriate to extinguish surrounding fire. Section 6 - ACCIDENTAL RELEASE MEASURES General Information: Use proper personal protective equipment as indicated in Section 8. Spills/Leaks: Clean up spills immediately, observing precautions in the Protective Equipment section. Sweep up, then place into a suitable container for disposal. Avoid generating dusty conditions. Provide ventilation. Section 7 - HANDLING and STORAGE Handling: Wash thoroughly after handling. Remove contaminated clothing and wash before reuse. Use only in a well-ventilated area. Minimize dust generation and accumulation. Do not get in eyes, on skin, or on clothing. Keep container tightly closed. Do not ingest or inhale. Storage: Do not store in direct sunlight. Keep container closed when not in use. Store in a cool, dry, well-ventilated area away from incompatible substances. Hormones and antibiotics room. Store below 40C. 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 general or local exhaust ventilation to keep airborne concentrations below the permissible exposure limits. Exposure Limits CAS# 50-07-7: CAS# 7647-14-5: Russia: 5 mg/m3 TWA Personal Protective Equipment Eyes: Wear safety glasses and chemical goggles if splashing is possible. Skin: Wear appropriate protective gloves and clothing to prevent skin exposure. Clothing: Wear appropriate protective clothing to minimize contact with skin. Respirators: A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use. Section 9 - PHYSICAL AND CHEMICAL PROPERTIES Physical State: Crystalline powder Color: blue-violet Odor: None reported. pH: Not available. Vapor Pressure: Not available. Viscosity: Not available. Boiling Point: Not available. Freezing/Melting Point: > 360 deg C Autoignition Temperature: Not applicable. Flash Point: Not applicable. Explosion Limits, lower: Not available. Explosion Limits, upper: Not available. Decomposition Temperature: Solubility in water: soluble Specific Gravity/Density: Molecular Formula: C15H18N4O5 Molecular Weight: 334.32 Section 10 - STABILITY AND REACTIVITY Chemical Stability: Stable under normal temperatures and pressures. Conditions to Avoid: Incompatible materials, light, dust generation, excess heat, temperatures above 40C. Incompatibilities with Other Materials: Strong oxidizing agents - strong acids - strong bases. Hazardous Decomposition Products: Nitrogen oxides, carbon monoxide, carbon dioxide, nitrogen. Hazardous Polymerization: Has not been reported. Section 11 - TOXICOLOGICAL INFORMATION RTECS#: CAS# 50-07-7: CN0700000 CAS# 7647-14-5: VZ4725000 LD50/LC50: CAS# 50-07-7: Oral, mouse: LD50 = 23 mg/kg; Oral, rat: LD50 = 30 mg/kg. CAS# 7647-14-5: Draize test, rabbit, eye: 100 mg Mild; Draize test, rabbit, eye: 100 mg/24H Moderate; Draize test, rabbit, eye: 10 mg Moderate; Draize test, rabbit, skin: 50 mg/24H Mild; Draize test, rabbit, skin: 500 mg/24H Mild; Inhalation, rat: LC50 = >42 gm/m3/1H; Oral, mouse: LD50 = 4 gm/kg; Oral, rat: LD50 = 3000 mg/kg; Skin, rabbit: LD50 = >10 gm/kg. Carcinogenicity: Mitomycin C - California: carcinogen, initial date 4/1/88 IARC: Group 2B carcinogen Sodium chloride - Not listed by ACGIH, IARC, or NTP. Other: See actual entry in RTECS for complete information. 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 Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.* Hazard Class: 6.1 UN Number: 2811 Packing Group: II IMO Shipping Name: TOXIC SOLID, ORGANIC, N.O.S. Hazard Class: 6.1 UN Number: 2811 Packing Group: II RID/ADR Shipping Name: TOXIC SOLID, ORGANIC, N.O.S. Hazard Class: 6.1 UN Number: 2811 Packing group: II USA RQ: CAS# 50-07-7: 10 lb final RQ; 4.54 kg final RQ Section 15 - REGULATORY INFORMATION European/International Regulations European Labeling in Accordance with EC Directives Hazard Symbols: T Risk Phrases: R 25 Toxic if swallowed. R 33 Danger of cumulative effects. Safety Phrases: S 45 In case of accident or if you feel unwell, seek medical advice immediately (show the label where possible). WGK (Water Danger/Protection) CAS# 50-07-7: 3 CAS# 7647-14-5: 0 Canada CAS# 50-07-7 is listed on Canada's NDSL List. CAS# 7647-14-5 is listed on Canada's DSL List. CAS# 50-07-7 is not listed on Canada's Ingredient Disclosure List. CAS# 7647-14-5 is not listed on Canada's Ingredient Disclosure List. US FEDERAL TSCA CAS# 50-07-7 is listed on the TSCA inventory. CAS# 7647-14-5 is listed on the TSCA inventory. SECTION 16 - ADDITIONAL INFORMATION N/A |
| 符号 |
GHS06, GHS08 |
|---|---|
| 信号词 | Danger |
| 危害声明 | H300-H351 |
| 警示性声明 | P201-P202-P280-P301 + P310 + P330-P308 + P313-P501 |
| 个人防护装备 | Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges |
| 危害码 (欧洲) | T:Toxic |
| 风险声明 (欧洲) | R25;R40 |
| 安全声明 (欧洲) | S36/37-S45-S28A-S28 |
| 危险品运输编码 | UN 3462 6.1/PG 2 |
| WGK德国 | 3 |
| RTECS号 | CN0700000 |
| 包装等级 | II |
| 危险类别 | 6.1(a) |
|
~10%
50-07-7 |
| 文献：Kasai; Kono; Ikeda; Yoda; Hirayama Journal of Organic Chemistry, 1992 , vol. 57, # 26 p. 7296 - 7299 |
|
~81%
50-07-7 |
| 文献：Arai, Hitoshi; Kasai, Masaji Journal of Organic Chemistry, 1993 , vol. 58, # 15 p. 4151 - 4152 |
|
~73%
50-07-7 |
| 文献：Kasai; Kono; Ikeda; Yoda; Hirayama Journal of Organic Chemistry, 1992 , vol. 57, # 26 p. 7296 - 7299 |
|
~%
50-07-7 |
| 文献：Kasai; Kono; Ikeda; Yoda; Hirayama Journal of Organic Chemistry, 1992 , vol. 57, # 26 p. 7296 - 7299 |
|
~79%
50-07-7 |
| 文献：Furuhata; Komiyama; Takeda; Takayanagi; Torii; Mishima; Ogura; Hata Chemical and Pharmaceutical Bulletin, 1989 , vol. 37, # 10 p. 2651 - 2654 |
|
~20%
50-07-7
详细
|
| 文献：Vyas, D. M.; Chiang, Y.; Benigni, D.; Doyle, T. W. Journal of Organic Chemistry, 1987 , vol. 52, # 25 p. 5601 - 5605 |
|
~%
50-07-7 |
| 文献：Senter; Pearce; Greenfield Journal of Organic Chemistry, 1990 , vol. 55, # 9 p. 2975 - 2978 |
|
~%
50-07-7 |
| 文献：Chen; Coppola; Johns; Bogardus; Lipper Journal of Pharmaceutical Sciences, 1986 , vol. 75, # 2 p. 208 - 210 |
|
~%
50-07-7 |
| 文献：Danishefsky; Ciufolini Journal of the American Chemical Society, 1984 , vol. 106, # 21 p. 6424 - 6425 |
| 上游产品 6 | |
|---|---|
| 下游产品 5 | |
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