18378-89-7

• 常用中文名：光辉霉素
• 常用英文名：Mithramycin A
• CAS号：18378-89-7
• 分子式：C₅₂H₇₆O₂₄
• 分子量：1085.145
• 相关类别： 原料药 抗肿瘤药 抗生素类抗肿瘤药
• 发布时间：2018-08-16 11:53:43
• 更新时间：2024-01-02 11:34:05
• Plicamycin 是一种选择性特 Sp1 转录因子抑制剂。Plicamycin 通过降低 Sp1 蛋白表达来抑制癌细胞生长。

名称

• 中文名: 光辉霉素
• 英文名: mithramycin
• 中文别名: 光神霉素; 金霉酸; 金霉酸; 普卡酶素
• 英文别名: Antibiotic LA-7017; D-threo-2-Pentulose, 5-deoxy-1-C-[(2S,3S)-7-[[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy]-3-[[O-2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1->3)-O-2,6-dideoxy-β-D-arabino-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy]-1,2,3,4-tetrahydro-5,10-dihydroxy-6-methyl-4-oxo-2-anthracenyl]-1-O-methyl-, (1S)-; aurlelicacid; MFCD00135618; EINECS 232-455-8; MITHRAMYCIN; Mithramycin A From Streptomyces Argillaceus; aurelicacid; (1S)-5-Deoxy-1-C-[(2S,3S)-7-{[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy}-3-{[2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy}-5,10-dihydroxy-6-methyl-4-oxo-1,2,3,4-tetrahydroanthracen-2-yl]-1-O-methyl-D-xylulose; (1S)-5-Deoxy-1-C-[(2R,3S)-7-{[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy}-3-{[2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy}-5,10-dihydroxy-6-methyl-4-oxo-1,2,3,4-tetrahydroanthracen-2-yl]-1-O-methyl-D-xylulose; PlicatoMycin; a-2371; D-threo-2-Pentulose, 5-deoxy-1-C-[(3S)-7-[[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy]-3-[[O-2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1->3)-O-2,6 -dideoxy-β-D-arabino-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy]-1,2,3,4-tetrahydro-5,10-dihydroxy-6-methyl-4-oxo-2-anthracenyl]-1-O-methyl-, (1S)-; mitramycin; (1S)-5-Deoxy-1-C-[(3S)-7-{[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy}-3-{[2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arab ino-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy}-5,10-dihydroxy-6-methyl-4-oxo-1,2,3,4-tetrahydro-2-anthracenyl]-1-O-methyl-D-xylulose; (1S)-5-Deoxy-1-C-[(2R,3S)-7-{[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-lyxo-hexopyranosyl]oxy}-3-{[2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl-(1->3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy}-5,10-dihydroxy-6-methyl-4-oxo-1,2,3,4-tetrahydro-2-anthracenyl]-1-O-methyl-D-xylulose; pa144; AURLELIC ACID; Aurelic acid; PLICAMYCIN; MITHRACIN; Mithramycin A,(1S)-5-Deoxy-1-C-[(2S,3S)-7-[[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-arabino-hexopyranosyl]oxy]-3-[(O-2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1.fwdarw.3)-O-2,6-dideoxy-β-D-lyxo-hexopyranosyl-(1.fwdarw.3)-2,6-dideo; aureolic acid; Mithramycin A

物化性质

• 密度: 1.5±0.1 g/cm3
• 沸点: 1169.8±65.0 °C at 760 mmHg
• 熔点: 180-183ºC
• 分子式: C₅₂H₇₆O₂₄
• 分子量: 1085.145
• 闪点: 327.4±27.8 °C
• 精确质量: 1084.472656
• PSA: 358.20000
• LogP: 1.29
• 外观性状: 黄色粉末
• 蒸汽压: 0.0±0.3 mmHg at 25°C
• 折射率: 1.640
• 分子结构:

  1、 摩尔折射率：262.26

  2、 摩尔体积（m³/mol）：728.3

  3、 等张比容（90.2K）：2174.2

  4、 表面张力（dyne/cm）：79.4

  5、 极化率（10^-24cm³）：103.96

• 计算化学:

  1、 疏水参数计算参考值（XlogP）：0.6

  2、 氢键供体数量：11

  3、 氢键受体数量：24

  4、 可旋转化学键数量：15

  5、 互变异构体数量：700

  6、 拓扑分子极性表面积（TPSA）：358

  7、 重原子数量：76

  8、 表面电荷：0

  9、 复杂度：1940

  10、 同位素原子数量：0

  11、 确定原子立构中心数量：25

  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：由链霉菌Streptomyces tanashiensis或S.684号菌株培养液体中提取的抗生素。鲜黄色结晶

  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）：180-183

  5. 沸点（ºC,常压）：不确定

  6. 沸点（ºC, 5.2kPa）：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,25ºC）：不确定

  12. 饱和蒸气压（kPa,60ºC）：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：易溶于水、丙酮、醇、氯仿，微溶于苯及乙醚。对光不稳定，水溶液在冰箱中保存稳定

生物活性

• 描述: Plicamycin 是一种选择性特 Sp1 转录因子抑制剂。Plicamycin 通过降低 Sp1 蛋白表达来抑制癌细胞生长。
• 相关类别:
  信号通路 >> 细胞周期/DNA损伤 >> DNA/RNA合成
  研究领域 >> 癌症
• 靶点:

  Sp1 transcription factor[1]

• 体外研究: Sp1是锌指转录因子,其通过控制参与细胞周期,细胞凋亡和DNA损伤的基因的表达来调节多种细胞功能并促进肿瘤进展。 Sp1与启动子的富含GC的基序结合,并与一般转录机制的组分和多种信号传导途径的共激活因子复合物相互作用。 Plicamycin(Mith)通过诱导蛋白酶体依赖性降解来降低Sp1蛋白,从而通过DR5/caspase-8/Bid信号通路抑制宫颈癌生长。为了评估普利霉素对宫颈癌细胞的抗增殖作用,在不同浓度的普利霉素处理或不处理的情况下培养具有不同遗传背景的两种宫颈癌细胞系。 48小时后,Plicamycin以浓度依赖性方式抑制HEp-2和KB细胞生长。通过DAPI染色对核浓缩和片段化定性估计凋亡细胞死亡。与未处理的对照相比,Plicamycin导致显着的DNA片段化[1]。
• 体内研究: 在异种移植模型中测定Plicamycin的抗肿瘤活性(0.2mg/kg /天)并观察肿瘤体积和重量的减少。在Plicamycin处理组中未观察到显着的小鼠体重减轻,表明Plicamycin相关的毒性是最小的。 Plicamycin还增加肿瘤异种移植物中的TUNEL阳性细胞。在器官中没有观察到显着的组间差异,表明本研究中使用的Plicamycin剂量没有明显的全身毒性迹象[1]。
• 细胞实验: HEp-2细胞和KB细胞在100μl/ ml的青霉素和链霉素和10％FBS的DMEM中培养，用于HEp-2细胞，5％FBS用于KB，在含有5％CO 2的潮湿气氛中于37℃培养。接种相同数量的细胞并使其附着。在50-60％汇合时，用DMSO或指定浓度的Plicamycin处理细胞（对于HEp-2细胞为50,100和200nM;对于KB细胞为20,40和80nM）。使用CellTiter 96 Aqueous One Solution Cell Proliferation Assay Kits测定细胞活力。简而言之，将细胞接种在96孔板中并与Plicamycin一起孵育。处理后，向每个孔中加入30μLMTS溶液，并将细胞在37℃下孵育2小时。使用酶标仪在490nm和690nm处分析MTS溶液[1]。
• 动物实验: 小鼠[1]使用雌性裸鼠。将KB细胞悬浮在无菌PBS中并皮下注射到小鼠的右侧腹中。将小鼠随机分成两组，每组含有5只小鼠，每周三次用0.2mg / kg /天的Plicamycin（ip）处理29天。对照小鼠接受相同体积的载体。 29天后，称重身体，器官和肿瘤并确定肿瘤体积。测量肿瘤[1]。
• 参考文献:

  [1]. Choi ES, et al. Modulation of specificity protein 1 by mithramycin A as a novel therapeutic strategy for cervical cancer. Sci Rep. 2014 Nov 24;4:7162.

MSDS

Name: Mithramycin 90% (HPLC) Material Safety Data Sheet Synonym: Aureolic Acid; Plicamycin CAS: 18378-89-7 Section 1 - Chemical Product MSDS Name:Mithramycin 90% (HPLC) Material Safety Data Sheet Synonym:Aureolic Acid; Plicamycin Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS CAS# Chemical Name content EINECS# 18378-89-7 Plicamycin 90 unlisted Hazard Symbols: T Risk Phrases: 23/24/25 Section 3 - HAZARDS IDENTIFICATION EMERGENCY OVERVIEW Toxic by inhalation, in contact with skin and if swallowed. Potential Health Effects Eye: May cause eye irritation. Skin: May cause skin irritation. Ingestion: May cause irritation of the digestive tract. Moderately toxic to humans by ingestion. The toxicological properties of this substance have not been fully investigated. May cause anemia, leukopenia (reduction in the number of white blood cells in the blood), and thrombocytopenia. 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: 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: Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water. 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: 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 agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate 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. Remove contaminated clothing and wash before reuse. Use with adequate ventilation. Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation. Storage: Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances. 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# 18378-89-7: 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: 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: Powder Color: yellow crystalline powder Odor: none reported pH: Not available. Vapor Pressure: Not available. Viscosity: Not available. Boiling Point: Not available. Freezing/Melting Point: 180.00 - 183.00 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 in water Specific Gravity/Density: Molecular Formula: C52H76O24 Molecular Weight: 1085.16 Section 10 - STABILITY AND REACTIVITY Chemical Stability: Stable under normal temperatures and pressures. Conditions to Avoid: Incompatible materials, dust generation, excess heat, strong oxidants. Incompatibilities with Other Materials: Oxidizing agents. Hazardous Decomposition Products: Carbon monoxide, irritating and toxic fumes and gases, carbon dioxide. Hazardous Polymerization: Has not been reported Section 11 - TOXICOLOGICAL INFORMATION RTECS#: CAS# 18378-89-7: PZ2800000 LD50/LC50: CAS# 18378-89-7: Oral, mouse: LD50 = 500 mg/kg. TDLo -Oral, Human: 50 Carcinogenicity: Plicamycin - 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: III IMO Shipping Name: TOXIC SOLID, ORGANIC, N.O.S. Hazard Class: 6.1 UN Number: 2811 Packing Group: III RID/ADR Shipping Name: TOXIC SOLID, ORGANIC, N.O.S. Hazard Class: 6.1 UN Number: 2811 Packing group: III Section 15 - REGULATORY INFORMATION European/International Regulations European Labeling in Accordance with EC Directives Hazard Symbols: T Risk Phrases: R 23/24/25 Toxic by inhalation, in contact with skin and if swallowed. Safety Phrases: S 28A After contact with skin, wash immediately with plenty of water. S 36/37/39 Wear suitable protective clothing, gloves and eye/face protection. S 37 Wear suitable gloves. S 38 In case of insufficient ventilation, wear suitable respiratory equipment. 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# 18378-89-7: No information available. Canada None of the chemicals in this product are listed on the DSL/NDSL list. CAS# 18378-89-7 is not listed on Canada's Ingredient Disclosure List. US FEDERAL TSCA CAS# 18378-89-7 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

CHEMICAL IDENTIFICATION RTECS NUMBER : PZ2800000 CHEMICAL NAME : Mithramycin CAS REGISTRY NUMBER : 18378-89-7 LAST UPDATED : 199609 DATA ITEMS CITED : 27 MOLECULAR FORMULA : C52-H76-O24 MOLECULAR WEIGHT : 1085.28 WISWESSER LINE NOTATION : L C666 DVT&&J BQ FYO1&VYQYQ1 M1 NQ LO- BT6OTJ EQ F1 DO- BT6OTJ DQ EQ F1&& EO- BT6OTJ EQ F1 DO HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Human DOSE/DURATION : 50 ug/kg/5D TOXIC EFFECTS : Blood - thrombocytopenia TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 2500 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 3100 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1741 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 500 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1090 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 2810 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 350 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LDLo - Lowest published lethal dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 2 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 250 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rabbit DOSE/DURATION : 250 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 2400 mg/kg/4W-I TOXIC EFFECTS : Liver - change in gall bladder structure or function Blood - hemorrhage Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Primate - monkey DOSE/DURATION : 2400 mg/kg/4W-I TOXIC EFFECTS : Blood - hemorrhage Blood - other changes Related to Chronic Data - death TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported DOSE : 2 mg/kg SEX/DURATION : female 11 day(s) after conception TOXIC EFFECTS : Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) MUTATION DATA TEST SYSTEM : Rodent - hamster DOSE/DURATION : 1250 ug/kg/5D (Continuous) REFERENCE : ENMUDM Environmental Mutagenesis. (New York, NY) V.1-9, 1979-87. For publisher information, see EMMUEG. Volume(issue)/page/year: 4,231,1982 *** REVIEWS *** TOXICOLOGY REVIEW 32XPAD "Teratology," Berry, C.L., and D.E. Poswillo, eds., New York, Springer, 1975 Volume(issue)/page/year: -,49,1975 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X3731 No. of Facilities: 290 (estimated) No. of Industries: 1 No. of Occupations: 8 No. of Employees: 6594 (estimated) No. of Female Employees: 2796 (estimated)

安全

• 符号: GHS07
• 信号词: Warning
• 危害声明: H302
• 个人防护装备: dust mask type N95 (US);Eyeshields;Faceshields;Gloves
• 危害码 (欧洲): Xn: Harmful;
• 风险声明 (欧洲): R22
• 安全声明 (欧洲): 45-38-36/37/39-28A-22
• 危险品运输编码: UN 3249
• WGK德国: 3
• RTECS号: PZ2800000
• 包装等级: III
• 危险类别: 6.1(b)