50-07-7

• 常用中文名：丝裂霉素C
• 常用英文名：Mitomycin C
• CAS号：50-07-7
• 分子式：C₁₅H₁₈N₄O₅
• 分子量：334.327
• 相关类别： 原料药 抗肿瘤药 抗生素类抗肿瘤药
• 发布时间：2018-04-14 08:00:00
• 更新时间：2024-01-02 15:55:06
• 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)。

名称

• 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

物化性质

• 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

生物活性

• 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:
  信号通路 >> 抗体- 药物偶联物 >> ADC细胞毒素
  信号通路 >> 自噬 >> 自噬
  信号通路 >> 细胞周期/DNA损伤 >> DNA烷基化剂/交联剂
  信号通路 >> 细胞周期/DNA损伤 >> DNA/RNA合成
  研究领域 >> 癌症
  天然产物 >> 其他
• 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:

  [1]. Cheng H, et al. Mitomycin C potentiates TRAIL-induced apoptosis through p53-independent upregulation of death receptors: Evidence for the role of c-Jun N-terminal kinase activation. Cell Cycle. 2012 Sep 1;11(17): 3312-23.

  [2]. Abbas T, et al. Differential activation of p53 by the various adducts of mitomycin C. J Biol Chem. 2002 Oct 25;277(43):40513-9.

  [3]. Michielsen D, et al. Mitomycin C and epirubicin: functional bladder damage in rats after repeat intravesical instillations. J Urol. 2005 Jun;173(6):2166-70.

MSDS

Name: Mitomycin C (Contains 2mg Mitomycin C and 48mg Sodium Chloride) Material Safety Data Sheet Synonym: Ametycine CAS: 50-07-7 Section 1 - Chemical Product MSDS Name:Mitomycin C (Contains 2mg Mitomycin C and 48mg Sodium Chloride) Material Safety Data Sheet Synonym:Ametycine Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS CAS# Chemical Name content EINECS# 50-07-7 Mitomycin C 4 200-008-6 Hazard Symbols: T 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

安全

• 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)

合成路线

110934-24-2 ~10% 50-07-7

文献：Kasai; Kono; Ikeda; Yoda; Hirayama Journal of Organic Chemistry, 1992 , vol. 57, # 26 p. 7296 - 7299

122644-74-0 ~81% 50-07-7

文献：Arai, Hitoshi; Kasai, Masaji Journal of Organic Chemistry, 1993 , vol. 58, # 15 p. 4151 - 4152

91917-64-5 ~73% 50-07-7

文献：Kasai; Kono; Ikeda; Yoda; Hirayama Journal of Organic Chemistry, 1992 , vol. 57, # 26 p. 7296 - 7299

132732-87-7 ~% 50-07-7

文献：Kasai; Kono; Ikeda; Yoda; Hirayama Journal of Organic Chemistry, 1992 , vol. 57, # 26 p. 7296 - 7299

128583-70-0 ~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

88948-91-8 91-00-9 ~20% 50-07-7 88949-01-3 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

126900-78-5 ~% 50-07-7

文献：Senter; Pearce; Greenfield Journal of Organic Chemistry, 1990 , vol. 55, # 9 p. 2975 - 2978

88949-01-3 ~% 50-07-7

文献：Chen; Coppola; Johns; Bogardus; Lipper Journal of Pharmaceutical Sciences, 1986 , vol. 75, # 2 p. 208 - 210

92056-69-4 ~% 50-07-7

文献：Danishefsky; Ciufolini Journal of the American Chemical Society, 1984 , vol. 106, # 21 p. 6424 - 6425

上下游产品

上游产品  6
110934-24-2 122644-74-0 91917-64-5 132732-87-7
91-00-9 88949-01-3
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4055-39-4 27066-44-0 801-52-5 129784-04-9
7041-61-4

制备

用发酵方法生产。自放线菌（Strepto-myces caespitosus）培养液可提出丝裂霉素A、B、C。我国从自己分离的放线菌H2760菌株中提取，又称自力霉素，与国外报道的丝裂霉素C相同。