actinomycin D | 77287-16-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: actinomycin D
• 英文别名: dactinomycin；2-amino-4,6-dimethyl-3-oxo-1-N,9-N-bis[7,11,14-trimethyl-2,5,9,12,15-pentaoxo-3,10-di(propan-2-yl)-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]phenoxazine-1,9-dicarboxamide；actinomycin-D；2-amino-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxylic acid bis-((17aS)-5c,12t-diisopropyl-9c,13,16-trimethyl-4,7,11,14,17-pentaoxo-(17ar)-hexadecahydro-10-oxa-3a,6,13,16-tetraaza-cyclopentacyclohexadecen-8c-ylamide)；actinomycin-C₁；Cosmegen
• CAS: 77287-16-2
• 化学式: C₆₂H₈₆N₁₂O₁₆
• 分子量: 1255.44
• InChiKey: RJURFGZVJUQBHK-UHFFFAOYSA-N

物化性质

• 沸点：
  1386.0±65.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)
• 物理描述：
  Actinomycin d appears as bright red rhomboid prisms or red powder. (NTP, 1992)
• 颜色/状态：
  Bright red crystalline powder
• 熔点：
  Melts between 245 and 248 dec C with decomposition.
• 溶解度：
  1 gram dissolves in about 8 mL of alcohol and 25 mL of water at 10 °C. 1 gram dissolves in 1000 mL of water at 37 °C and about 1666 mL of ether.
• 蒸汽压力：
  0 mm Hg at 25 °C (est)
• 稳定性/保质期：

  Dilute soln are very sensitive to light /Trihydrate/

• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
• 解离常数：
  pKa = 11.90

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  90
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  356
• 氢给体数：
  5
• 氢受体数：
  18

ADMET

代谢

达克替康似乎只有轻微代谢；在尿液中检测到了少量药物的单内酯。

Dactinomycin appears to be only slightly metabolized; small amounts of monolactones of the drug have been detected in the urine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

人类致癌性证据不足。动物致癌性证据有限。总体评估：第3组：该物质对人类致癌性无法分类。

Inadequate evidence of carcinogenicity in humans. Limited evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌剂：放线菌素D

IARC Carcinogenic Agent:Actinomycin D

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第10卷：（1976年）一些天然存在的物质

IARC Monographs:Volume 10: (1976) Some Naturally Occurring Substances

来源:International Agency for Research on Cancer (IARC)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间的使用总结：目前没有关于在母乳喂养期间使用放线菌素的信息。大多数来源认为，在母亲抗肿瘤药物治疗期间，母乳喂养是禁忌的。制造商建议在放线菌素治疗期间及最后一次给药后14天内停止母乳喂养。 ◉ 对哺乳婴儿的影响：截至修订日期，没有找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，没有找到相关的已发布信息。

◉ Summary of Use during Lactation:No information is available on the use of dactinomycin during breastfeeding. Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. The manufacturer recommends that breastfeeding be discontinued during dactinomycin therapy and for 14 days after the last dose. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

吸收、分配和排泄

链霉素从胃肠道吸收不良。该药物对组织极为刺激，因此必须静脉给药。

Dactinomycin is poorly absorbed from the GI tract. The drug is extremely irritating to tissues and, therefore, must be administered iv.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

放线菌素D迅速分布到组织中，在骨髓和带核细胞（包括粒细胞和淋巴细胞）中浓度较高。该药物似乎很难穿越血脑屏障，或者根本不能穿越。

Dactinomycin is rapidly distributed into tissues, with high concentrations in bone marrow and nucleated cells, including granulocytes and lymphocytes. The drug appears to cross the blood-brain barrier poorly, if at all.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

柔红霉素的血浆蛋白结合率是5%。

Plasma protein binding /of dactinomycin/ is 5%.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

显然，放线菌素D会穿过胎盘。目前尚不清楚放线菌素D是否会分布到乳汁中。

Dactinomycin apparently crosses the placenta. It is not known if dactinomycin is distributed into milk.

来源:Hazardous Substances Data Bank (HSDB)

文献信息

• [EN] SUBSTITUTED N-HETEROCYCLIC CARBOXAMIDES AS ACID CERAMIDASE INHIBITORS AND THEIR USE AS MEDICAMENTS<br/>[FR] CARBOXAMIDES N-HÉTÉROCYCLIQUES SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA CÉRAMIDASE ACIDE ET LEUR UTILISATION EN TANT QUE MÉDICAMENTS
  申请人：BIAL BIOTECH INVEST INC

  公开号：WO2021055627A1

  公开（公告）日：2021-03-25

  The invention provides substituted N-heterocyclic carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat a medical disorder, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.

  这项发明提供了替代的N-杂环羧酰胺和相关化合物，含有这些化合物的组合物，医疗工具包，以及使用这些化合物和组合物治疗患者的医疗疾病（例如癌症、溶酶体贮积症、神经退行性疾病、炎症性疾病）的方法。
• SULFONAMIDE, SULFAMATE, AND SULFAMOTHIOATE DERIVATIVES
  申请人：Wang Zhong

  公开号：US20120077814A1

  公开（公告）日：2012-03-29

  The disclosure provides biologically active compounds of formula (I): and pharmaceutically acceptable salts thereof, compositions containing these compounds, and methods of using these compounds in a variety applications, such as treatment of diseases or disorders associated with E1 type activating enzymes, and with Nedd8 activating enzyme (NAE) in particular.

  该披露提供了化学式(I)的生物活性化合物及其药用盐，含有这些化合物的组合物，以及在各种应用中使用这些化合物的方法，例如用于治疗与E1型激活酶相关的疾病或紊乱，特别是与Nedd8激活酶(NAE)相关的疾病或紊乱。
• [EN] COMPOUNDS AND METHODS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：TAVARES FRANCIS XAVIER

  公开号：WO2016168118A1

  公开（公告）日：2016-10-20

  Novel compounds of formula (II) are disclosed. Compounds of formula (II) comprise ornithine derivatives or compounds that may metabolize to ornithine. Also disclosed are methods for the treatment of neurodegenerative diseases such as Alzheimer's Disease using compounds of formula (II).

  公开了化学式（II）的新化合物。化学式（II）的化合物包括鸟氨酸衍生物或可能代谢成鸟氨酸的化合物。还公开了使用化学式（II）的化合物治疗神经退行性疾病，如阿尔茨海默病的方法。
• Eflornithine Prodrugs, Conjugates and Salts, and Methods of Use Thereof
  申请人：Xu Feng

  公开号：US20100120727A1

  公开（公告）日：2010-05-13

  In one aspect, the present invention provides a composition of a covalent conjugate of an eflornithine analog with an anti-inflammatory drug. In another aspect, the present invention provides a composition of an eflornithine prodrug. In another aspect, the present invention provides a composition of an eflornithine or its derivatives aspirin salt. In another aspect, the present invention provides methods for treating or preventing cancer using the conjugates or salts of eflornithine analogs or eflornithine prodrugs.

  在一个方面，本发明提供了一种氟硝西汀类似物与抗炎药物的共价结合物的组合物。在另一个方面，本发明提供了一种氟硝西汀前药的组合物。在另一个方面，本发明提供了一种氟硝西汀或其衍生物水杨酸盐的组合物。在另一个方面，本发明提供了使用氟硝西汀类似物或氟硝西汀前药的共轭物或盐来治疗或预防癌症的方法。
• [EN] PREPARATION AND USES OF REACTIVE OXYGEN SPECIES SCAVENGER DERIVATIVES<br/>[FR] PRÉPARATION ET UTILISATIONS DE DÉRIVÉS PIÉGEURS D'ESPÈCES RÉACTIVES DE L'OXYGÈNE
  申请人：XW LAB INC

  公开号：WO2019033330A1

  公开（公告）日：2019-02-21

  Compounds of Formula (I) a or (I) b: including certain quinone derivatives, and the corresponding pharmaceutical compositions, which may serve to modulate ferroptosis in a subject. Also disclosed herein are the preparations of these compounds and pharmaceutical compositions and their potential uses in the manufacture of a medicament in reducing reactive oxygen species (ROS) in a cell and for preventing, treating, ameliorating certain related disorder or a disease.

  公式(I) a或(I) b的化合物：包括某些醌衍生物，以及相应的药物组合物，可以用于调节受试者中的铁死亡。本文还披露了这些化合物和药物组合物的制备方法，以及它们在制造药物中用于减少细胞中的活性氧化物（ROS）并预防、治疗、改善某些相关疾病或疾病的潜在用途。