客户使用产品发表文献 46 篇

▴ 折叠

产品文档

Quality Control & SDS

View current batch:

Purity: >98.00%

实验参考方法

Cell experiment [1]:
Cell lines	A10 cells (Vascular SMC)
Preparation Method	Dissolve actinomycin D in 0.1% DMSO and make 3 different concentration groups: 80 nM, 800 nM, 8 μM. Add various doses of actinomycin D to cultured SMC which have been starved for 24 h and incubate at 37 ℃. Drug treatment is carried out for 18-24 h. In the meantime, a vehicle control containing DMSO is also included.
Reaction Conditions	80 nM, 800 nM, 8 μM for 18-24h
Applications	Actinomycin D is a significant polypeptide antibiotic isolated from soil bacteria, Streptomyces. It inhibits DNA repair with IC50 of 0.42 μM and rests the cell cycle at G1 phase with IC50 of 0.4 nM.
Animal experiment [2]:
Animal models	C57BL/6 wild-type mice with Em-TCL-1 transgenic mice tumor cells
Preparation Method	The original Em-TCL1a transgenic mice have been backcrossed to C57BL/6 mice for 9 generations. Tumor cells from Em-TCL-1 transgenic mice were engrafted to C57BL/6 wild-type mice.
Dosage form	0.06 mg/kg, i.p.
Applications	Actinomycin D was chosen to further investigate as treatment option for CLL patients high-risk features, due to its activity in p53-aberrant CLL cells, known clinical properties, low IC50 and moderate toxicity. The presence of actinomycin D prevents the release of protective factors from the stroma cells. BCL2 mRNA downregulation in CLL is specific for actinomycin D treatment. Actinomycin D leads to tumor regression in this mouse model of CLL, and in two of four mice renewed lymphoma formation was prevented, strongly suggesting a potent role for actinomycin D in CLL treatment in humans.
References: [1]. Wu CH, et al. The molecular mechanism of actinomycin D in preventing neointimal formation in rat carotid arteries after balloon injury. J Biomed Sci. 2005;12(3):503-12. [2]. Merkel O. et al. Actinomycin D induces p53-independent cell death and prolongs survival in high-risk chronic lymphocytic leukemia. Leukemia (2012) 26, 2508–2516.

产品描述

Actinomycin D (dactinomycin) is a natural chromopeptide isolated from Streptomyces species, and has one heterocyclic chromophore and two cyclic pentapeptide lactone rings. [1] It is the first antibiotic showing anti-tumor activity, and has been implemented in the clinical practice for years to treat, such as testicular cancer, and choriocarcinoma.[2]

Actinomycin D intercalates into DNA to inhibit the transcription. It forms a very stable complex with DNA, preventing the unwinding of the DNA double-helix, so as to inhibit the DNA-dependent RNA polymerase activity. Actinomycin D is well implemented in mRNA stability assays to inhibit the synthesis of new mRNA, allowing the assessment of mRNA decay by measuring mRNA abundance following transcription inhibition. [3]

The in vitro experiment suggests that actinomycin D is an potent and effective agent to inhibit the proliferation of SMC by preventing cells from getting into S phase. The LD50 (260 lM) determined by measuring the remaining viable cells at various concentrations of actinomycin D was about five orders greater than that of IC50 (0.4 nM), which was calculated by measuring the percentage of cells in S phase following the treatment of actinomycin D. A dose-dependent inhibition by actinomycin D was found in PCNA, Raf and FAK. However, in contrast to those seen on PCNA, Raf and FAK expression, the phosphorylated Erk was significantly up-regulated by actinomycin D. An in vivo study using rat carotid artery as a model was conducted to evaluate if topically applied actinomycin D onto the arterial adventitia of the artery was effective in suppressing the formation of stenosis following a balloon angioplasty. Topical application of pluronic gel containing 80 nM and 80 μM actinomycin D to surround the adventitia of rat carotid arteries, the thickness of the neointima was significantly reduced (45% and 55%, respectively). [4]

Reference:
[1]. Farber S. Chemotherapy in the treatment of leukemia and Wilms' tumor. JAMA. 1966 Nov 21;198(8):826-36. PMID: 4288581.
[2]. Lewis J.L., Jr. Chemotherapy of gestational choriocarcinoma. Obstet. Gynecol. Surv. 1973;28:7478–7480. doi: 10.1097/00006254-197307000-00006.
[3]. Shyu A. B., Greenberg M. E. and Belasco J. G.(1989). The c-fos transcript is targeted for rapid decay by two distinct mRNA degradation pathways. Genes Dev 3(1): 60-72.
[4]. Wu, C. H., Pan, J. S., Chang, W. C., Hung, J. S., & Mao, S. J. T. (2005). The molecular mechanism of actinomycin D in preventing neointimal formation in rat carotid arteries after balloon injury. Journal of Biomedical Science, 12(3), 503–512. doi:10.1007/s11373-005-6900-5.

阿克替诺霉素D（也称为达克替诺霉素）是一种从链霉菌属中分离出来的天然色胺肽，含有一个杂环色团和两个五元环戊肽内酯环。它是第一种显示抗肿瘤活性的抗生素，并已经在临床实践中使用多年，用于治疗睾丸癌和绒毛膜癌等疾病。

阿克替诺霉素D插入到DNA中，抑制转录。它与DNA形成非常稳定的复合物，防止DNA双螺旋解开，从而抑制依赖于DNA的RNA聚合酶活性。阿克替诺霉素D在mRNA稳定性测定中得到了很好的应用，以抑制新mRNA的合成，并通过测量转录抑制后mRNA丰度来评估mRNA降解。[3]

实验室内的实验表明，阿克替霉素D是一种有效的药物，可以通过阻止细胞进入S期来抑制平滑肌细胞的增殖。通过测量不同剂量下剩余存活细胞数量确定的LD50（260微摩尔）比IC50（0.4纳摩尔），即使用阿克替霉素D处理后处于S期的细胞百分比计算得出的值小五个数量级。在PCNA、Raf和FAK中发现了依赖剂量作用。然而，与PCNA、Raf和FAK表达相反，在接受阿克替霉素D处理后磷酸化Erk显著上调。使用大鼠颈动脉作为模型进行体内研究，评估局部应用阿克替霉素D是否能够有效地抑制气囊扩张术后瘢痕形成。将含有80纳摩尔和80微米阿克替霉素D的聚乙二醇凝胶局部涂抹于大鼠颈动脉周围组织中时，新生内膜厚度显着降低（分别为45%和55%）。[4]

参考文献： [1]. Farber S. 化疗在治疗白血病和威尔姆斯肿瘤中的应用。JAMA. 1966年11月21日;198(8):826-36. PMID: 4288581. [2]. Lewis J.L., Jr. 妊娠性绒毛膜癌的化学治疗。Obstet.Gynecol.Surv.1973;28:7478–7480.doi：10.1097/00006254-197307000-00006。 [3]. Shyu A.B., Greenberg M.E.and Belasco J.G.(1989). c-fos转录本被两种不同的mRNA降解途径快速降解。Genes Dev 3(1):60-72。 [4]. Wu, C.H., Pan, J.S., Chang, W.C., Hung, J.S.& Mao,S.J.T.(2005).阿克替霉素D预防大鼠颈动脉球囊损伤后新内膜形成的分子机制。生物医学科学杂志，12（3），503–512。doi：10.1007/s11373-005-6900-5。

Chemical Properties

Cas No.	50-76-0	SDF
别名	放线菌素D,DACTINOMYCIN
化学名	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
Canonical SMILES	CC1C(C(=O)NC(C(=O)N2CCCC2C(=O)N(CC(=O)N(C(C(=O)O1)C(C)C)C)C)C(C)C)NC(=O)C3=C4C(=C(C=C3)C)OC5=C(C(=O)C(=C(C5=N4)C(=O)NC6C(OC(=O)C(N(C(=O)CN(C(=O)C7CCCN7C(=O)C(NC6=O)C(C)C)C)C)C(C)C)C)N)C
分子式	C₆₂H₈₆N₁₂O₁₆	分子量	1255.43
溶解度	≥ 62.75 mg/mL in DMSO	储存条件	Store at -20℃; protected from light
General tips	请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。
Shipping Condition	评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。

溶解性数据

制备储备液
		1 mg	5 mg	10 mg
	1 mM	0.7965 mL	3.9827 mL	7.9654 mL
	5 mM	0.1593 mL	0.7965 mL	1.5931 mL
	10 mM	0.0797 mL	0.3983 mL	0.7965 mL

摩尔浓度计算器
稀释计算器
分子量计算器

计算

动物体内配方计算器 (澄清溶液)

第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）

给药剂量

mg/kg

动物平均体重

g

每只动物给药体积

ul

动物数量

只

第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方）

% DMSO+ % + % Tween 80+ % saline

计算重置

计算结果:

工作液浓度： mg/ml；

DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系GLPBIO）；

体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。

注意：1. 首先保证母液是澄清的；
2. 一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。

Research Update

[Actinomycin D and its mechanisms of action]

Postepy Hig Med Dosw (Online)2005;59:290-8.PMID: 15995596DOI: 10.1080/14786419.2018.1431630

Actinomycin D is a well-known antibiotic of the actinomycin group that exhibits high antibacterial and antitumor activity. Actinomycin D has been widely used in clinical practice since 1954 as an anticancer drug for treating many tumors and it is also a useful tool in biochemistry and molecular biology. According to the Internet bibliographic database -- MEDLINE, actinomycins, and mainly actinomycin D, have been the subject of about 3300 science papers so far, and this paper is a review of the information concerning the mechanisms of action of actinomycin D. There are several mechanisms of its action that are responsible for its cytotoxic and antitumor action, these being associated with DNA functionality, leading to RNA and, consequently, protein synthesis inhibition. The two main mechanisms are intercalation to DNA and the stabilization of cleavable complexes of topoisomerases I and II with DNA, in which a phenoxazone ring localizes between GpC base pair sequence in DNA and polypeptide lactones rings occupy a position in the minor groove of the DNA helix or the drug penetrates to a place in the DNA structure where topoisomerase binds with DNA, respectively. Moreover, the slow dissociation of actinomycin D from DNA complexes, its photodynamic activity and free radical formation, as well as other biochemical effects of activity of actinomycin D may be, as suggested, important factors that influence the biological activity of this drug. In the literature not enough convincing evidence has been proposed that could indicate one particular mechanism of action as responsible for the biological activity of actinomycin D.

Antifungal effects of actinomycin D on Verticillium dahliae via a membrane-splitting mechanism

Nat Prod Res2019 Jun;33(12):1751-1755.PMID: 29382222DOI: 10.1080/14786419.2018.1431630

Antifungal bioassays led to the isolation of actinomycins D and A₁ from Streptomyces luteus TRM45540 collected from Norpo in Xinjiang, and these compounds were identified by nuclear magnetic resonance spectroscopy. The antifungal activity of actinomycin D was higher than that of actinomycin A₁. Actinomycin D clearly inhibited the spore germination, hyphal growth and biomass accumulation of Verticillium dahliae in a dose-dependent manner. Flow cytometric analysis with propidium iodide, total ergosterol measurement, cell leakage and scanning electron microscopy experiments demonstrated that the plasma membrane of this fungus was damaged by actinomycin D, resulting in swollen cells and cellular content leakage. Transmission electron microscopy revealed that parts of the plasma membrane infolded after being treated with actinomycin D. The antifungal activity of actinomycin D damaged the fungal plasma membrane of V. dahliae via a membrane-splitting mechanism, which provided new insights into the functional mechanism of actinomycin D.

Multi-Omics Analysis Reveals Anti- Staphylococcus aureus Activity of Actinomycin D Originating from Streptomyces parvulus

Int J Mol Sci2021 Nov 12;22(22):12231.PMID: 34830114DOI: 10.3390/ijms222212231

Staphylococcus aureus (S. aureus) is a common pathogen that causes various serious diseases, including chronic infections. Discovering new antibacterial agents is an important aspect of the pharmaceutical field because of the lack of effective antibacterial drugs. In our research, we found that one anti-S. aureus substance is actinomycin D, originating from Streptomyces parvulus (S. parvulus); then, we further focused on the anti-S. aureus ability and the omics profile of S. aureus in response to actinomycin D. The results revealed that actinomycin D had a significant inhibitory activity on S. aureus with a minimum inhibitory concentration (MIC) of 2 μg/mL and a minimum bactericidal concentration (MBC) of 64 μg/mL. Bacterial reactive oxygen species (ROS) increased 3.5-fold upon treatment with actinomycin D, as was measured with the oxidation-sensitive fluorescent probe DCFH-DA, and H₂O₂ increased 3.5 times with treatment by actinomycin D. Proteomics and metabolomics, respectively, identified differentially expressed proteins in control and treatment groups, and the co-mapped correlation network of proteomics and metabolomics annotated five major pathways that were potentially related to disrupting the energy metabolism and oxidative stress of S. aureus. All findings contributed to providing new insight into the mechanisms of the anti-S. aureus effects of actinomycin D originating from S. parvulus.

[Modifications of actinomycin D structure as example of actinomycins structure-activity relationship]

Postepy Hig Med Dosw (Online)2005;59:276-82.PMID: 15995594DOI: 10.3802/jgo.2019.30.e87

For over 60 years, actinomycins, well-known antibacterial and anticancer antibiotics, have been the subject of the scientific research. These compounds exhibit high toxicity and therefore are not widely used in the chemotherapeutic treatment of antibacterial and antifungal diseases. However, actinomycin D, the best-known compound from the actinomycin group, has been introduced into clinical practice as an anticancer drug. Actinomycin D, together with 7-amino-actinomycin D, also became a useful tool in biochemistry and molecular biology. The isolation, production, chemistry, and biological and clinical use of the actinomycins have been thoroughly investigated. Many derivatives of actinomycins, differing in chemical structure as well as biological activity, have been isolated and synthesized and their modifications involved not only the chromphoric phenoxazone ring, but also two cyclic pentapeptide lacton rings. Modifications of the actinomycins' chromophore mainly concerned introducing an amino group in position 2 and a carbon atom in position 7, but also modifications in positions 4, 6, and 8 of the phenoxazone ring. The actinomycin peptide moiety was mainly modified by replacement of amino acids in the pentapeptide rings and also by the synthesis of actinomycin derivatives with open peptide lacton rings. These modifications enabled separating the elements in the actinomycin structure which are responsible for the biological activity of these compounds. That was key information for recognizing the performance of these compounds, and an important way of planning effective new chemotherapeutics.

Actinomycin D shortage in the Brazilian market: new challenges for successful treatment of gestational trophoblastic neoplasia

J Gynecol Oncol2019 Jul;30(4):e87.PMID: 31074249DOI: 10.3802/jgo.2019.30.e87

Objective: To compare the treatment outcome and cost-effectiveness of pulsed actinomycin D (Act-D) and 5-day Act-D in patients with low-risk gestational trophoblastic neoplasia (GTN).
Method: The present retrospective study included patients with low-risk GTN who received pulsed Act-D or 5-day Act-D as first-line chemotherapy at West China Second Hospital, Chengdu, China, between January 1, 2016, and December 31, 2017. Complete remission rates, mean number of treatment courses, and adverse events were compared, and a cost-effectiveness analysis was performed.
Results: The study included 34 patients treated with pulsed Act-D and 26 patients treated with 5-day Act-D. Overall complete remission was observed in 21 (62%) patients in the pulsed Act-D group and 19 (73%) patients in the 5-day Act-D group (P=0.355); the mean number of treatment courses were 5.1 and 5.3, respectively (P=0.686). When Act-D failed, patients in each group required 4.9 and 4.6 courses, respectively, of a multi-agent regimen (P=0.545). No major adverse events were observed but moderate adverse events were more frequent in the pulsed Act-D group (P=0.011). The 5-day Act-D regimen was more expensive compared with pulsed Act-D regimen (US$7504.33 vs $5541.79), with an incremental cost-effectiveness ratio of $64 557.08 per avoidance of treatment failure.
Conclusion: Pulsed Act-D was more cost-effective than 5-day Act-D and could be preferred when considering Act-D as chemotherapy for low-risk GTN.

Actinomycin D

Customer Reviews

B1