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Purity: ≥98%
Dactinomycin (Actinomycin IV; Actinomycin D), a compound of the actinomycine class, is a polypeptide antibiotic isolated from soil bacteria of the genus Streptomyces. It has an IC50 of 0.42 μM, which inhibits DNA repair. It is one of the more traditional chemotherapy medications and has been for a long time. The first antibiotic with anti-cancer properties was actinomycin D. Selman Waksman and his colleague H. B. Woodruff isolated it for the first time in 1940. On December 10, 1964, the US FDA gave it approval, and Merck Sharp and Dohme introduced it under the brand name Cosmegen.
| Targets |
Autophagy; cell cycle (IC50 = 0.4 nM); DNA repair (IC50 = 0.42 μM)
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| ln Vitro |
Actinomycin D inhibits BrdU incorporation at 80 nM, which significantly reduces SMC proliferation. Using a flowcytometric analysis, the G1-phase arrest provides more evidence for this. Actinomycin D suppresses the levels of focal adhesion kinase (FAK), proliferating cell nuclear antigen (PCNA), and Raf protein expression. Actinomycin D is found to increase extracellular signalregulated kinases (Erk) involved in cell-cycle arrest.[1]
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| ln Vivo |
Actinomycin D is active in two distinct mouse models that are typified by either an unmutated B-cell receptor or inactive p53 function, both of which are recognized adverse prognostic factors in CLL. Actinomycin D targets the survival proteins TOSO, BCL2, and MCL1.[3]
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| Enzyme Assay |
Actinomycin D is co-incubated for three hours at thirty degrees Celsius with a reaction mixture that has the following contents: 120 mg of a whole-cell extract of HeLa cells, 70 mM KCl, 0.4 mM of dGTP, dCTP, dATP, and digoxygenylated-dUTP in reaction buffer that has 40 mM Hepes-KOH (pH 7.6), 5 mM MgCl2, 0.5 mM Dithiotreitol, 2 mM EGTA, 10 mM phosphocreatine, 50 mg/mL creatine phosphate, and 360 mg/mL of bovine serum albumin combined. DNA damage is identified during this reaction, and neosynthesized DNA fragments replace the removed patches. Digoxygenylated-dUMPs are integrated during this DNA synthesis. Three washes halt the DNA repair reaction.
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| Cell Assay |
Actinomycin D at different doses is incubated at 37°C after cultured SMC are starved for 24 hours. 18 to 24 hours are spent on drug treatment. Since actinomycin D dissolves in 0.1% DMSO, DMSO-containing vehicle control is also provided.
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| Animal Protocol |
Mice: For more than nine generations, the original Eμ-TCL1a transgenic mice have been backcrossed to C57BL/6 mice.The Eμ-TCL-1 transgenic mice's tumor cells are engrafted into C57BL/6 wild-type mice. Mice are regularly given blood from the tail vein, which is then subjected to flow cytometry analysis to determine the percentage of CD5+/CD19+ cells in the peripheral blood. Treatment is initiated when 40–60% of the tumor cells in the peripheral blood are present. IV injections of actinomycin D (0.06 mg/kg over 10 days) are administered every day.
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| References | |
| Additional Infomation |
Actinomycin d appears as bright red rhomboid prisms or red powder. (NTP, 1992)
National Toxicology Program, Institute of Environmental Health Sciences, National Institutes of Health (NTP). 1992. National Toxicology Program Chemical Repository Database. Research Triangle Park, North Carolina.
CAMEO Chemicals
Actinomycin D is an actinomycin. It has a role as a mutagen. ChEBI A compound composed of a two cyclic peptides attached to a phenoxazine that is derived from streptomyces parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015) DrugBank Dactinomycin is an Actinomycin. The mechanism of action of dactinomycin is as a Nucleic Acid Synthesis Inhibitor, and Protein Synthesis Inhibitor. FDA Pharm Classes Dactinomycin is an intravenously administered, antineoplastic antibiotic that is used in the treatment of solid tumors in children and choriocarcinoma in adult women. In high doses, dactinomycin can cause severe liver injury including sinusoidal obstruction syndrome. LiverTox Dactinomycin is a natural product found in Streptomyces, Streptomyces flavovirens, and other organisms with data available. LOTUS - the natural products occurrence database Dactinomycin is a chromopeptide antineoplastic antibiotic isolated from the bacterium Streptomyces parvulus. Dactinomycin intercalates between adjacent guanine-cytosine base pairs, blocking the transcription of DNA by RNA polymerase; it also causes single-strand DNA breaks, possibly via a free-radical intermediate or an interaction with topoisomerase II. (NCI04) NCI Thesaurus (NCIt) View MoreActinomycin D can cause cancer and developmental toxicity according to state or federal government labeling requirements. The CA Office of Environmental Health Hazard Assessment (OEHHA) A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015) Dactinomycin is an intravenously administered, antineoplastic antibiotic that is used in the treatment of solid tumors in children and choriocarcinoma in adult women. In high doses, dactinomycin can cause severe liver injury including sinusoidal obstruction syndrome. Generally, the actinomycins exert an inhibitory effect on gram-positive and gram-negative bacteria and on some fungi. However, the toxic properties of the actinomycins (including dactinomycin) in relation to antibacterial activity are such as to preclude their use as antibiotics in the treatment of infectious diseases. Because the actinomycins are cytotoxic, they have an antineoplastic effect which has been demonstrated in experimental animals with various types of tumor implant. This cytotoxic action is the basis for their use in the treatment of certain types of cancer. Dactinomycin is believed to produce its cytotoxic effects by binding DNA and inhibiting RNA synthesis. Absorption: poorly absorbed from gastrointestinal tract. Biological Half-Life: 36 hours. The capacity of actinomycins to bind with double-helical DNA is responsible for their biological activity and cytotoxicity. X-ray studies of a crystalline complex between dactinomycin and deoxyguanosine permitted formulation of a model that appears to explain the binding of the drug to DNA. The planar phenoxazone ring intercalates between adjacent guanine-cytosine base pairs of DNA, while the polypeptide chains extend along the minor groove of the helix. The summation of these interactions provides great stability to the dactinomycin-DNA complex, and as a result of the binding of dactinomycin, the transcription of DNA by RNA polymerase is blocked. The DNA-dependent RNA polymerases are much more sensitive to the effects of dactinomycin than are the DNA polymerases. In addition, dactinomycin causes single-strand breaks in DNA, possibly through a free-radical intermediate or as a result of the action of topoisomerase II. Dactinomycin is an antineoplastic antibiotic. The drug has bacteriostatic activity, particularly against gram-positive organisms, but its cytotoxicity precludes its use as an anti-infective agent. Although the exact mechanism(s) of action has not been fully elucidated, the drug appears to inhibit DNA-dependent RNA synthesis by forming a complex with DNA by intercalating with guanine residues and impairing the template activity of DNA. Protein and DNA synthesis are also inhibited but less extensively and at higher concentrations of dactinomycin than are needed to inhibit RNA synthesis. Dactinomycin is immunosuppressive and also possesses some hypocalcemic activity similar to plicamycin. |
| Molecular Formula |
C62H86N12O16
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|---|---|
| Molecular Weight |
1255.43
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| Exact Mass |
1254.63
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| Elemental Analysis |
C, 59.32; H, 6.90; N, 13.39; O, 20.39
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| CAS # |
50-76-0
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| PubChem CID |
457193
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| Appearance |
Orange to red solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
1386.0±65.0 °C at 760 mmHg
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| Melting Point |
251-253 °C
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| Flash Point |
792.1±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.656
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| Source |
Streptomyces
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| LogP |
3.8
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| tPSA |
356Ų
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| SMILES |
C[C@@H]1[C@@H](C(=O)N[C@@H](C(=O)N2CCC[C@H]2C(=O)N(CC(=O)N([C@H](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)N[C@H]6[C@H](OC(=O)[C@@H](N(C(=O)CN(C(=O)[C@@H]7CCCN7C(=O)[C@H](NC6=O)C(C)C)C)C)C(C)C)C)N)C
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| InChi Key |
RJURFGZVJUQBHK-IIXSONLDSA-N
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| InChi Code |
InChI=1S/C62H86N12O16/c1-27(2)42-59(84)73-23-17-19-36(73)57(82)69(13)25-38(75)71(15)48(29(5)6)61(86)88-33(11)44(55(80)65-42)67-53(78)35-22-21-31(9)51-46(35)64-47-40(41(63)50(77)32(10)52(47)90-51)54(79)68-45-34(12)89-62(87)49(30(7)8)72(16)39(76)26-70(14)58(83)37-20-18-24-74(37)60(85)43(28(3)4)66-56(45)81/h21-22,27-30,33-34,36-37,42-45,48-49H,17-20,23-26,63H2,1-16H3,(H,65,80)(H,66,81)(H,67,78)(H,68,79)/t33-,34-,36+,37+,42-,43-,44+,45+,48+,49+/m1/s1
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| Chemical Name |
2-amino-4,6-dimethyl-3-oxo-1-N,9-N-bis[(3R,6S,7R,10S,16S)-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
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| Synonyms |
DACT; ACTD; actinomycin C1; actinomycin D; actinomycin I1; actinomycin IV; actinomycin X 1; actinomycinthrvalprosarmeval; dactinomycine; meractinomycin; actinomycin D; Actinomycin C1; Actinomycin IV; Meractinomycin; 50-76-0; Cosmegen; Actinomycin I1; US brand names: Cosmegen; Lyovac.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 27 mg/mL (~21.5 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (1.66 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (1.66 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00352534 | Active Recruiting |
Biological: Dactinomycin Drug: Vincristine Sulfate |
Stage I Kidney Wilms Tumor Stage II Kidney Wilms Tumor |
Children's Oncology Group | October 30, 2006 | Phase 3 |
| NCT02567435 | Active Recruiting |
Drug: Vinorelbine Biological: Dactinomycin |
Rhabdomyosarcoma Alveolar Rhabdomyosarcoma |
National Cancer Institute (NCI) |
June 1, 2016 | Phase 3 |
| NCT01871766 | Active Recruiting |
Drug: Dactinomycin Drug: Vincristine |
Rhabdomyosarcoma | St. Jude Children's Research Hospital |
December 4, 2013 | Phase 2 |
| NCT01464606 | Active Recruiting |
Drug: Dactinomycin Drug: Vincristine |
Pleuropulmonary Blastoma | Children's Hospitals and Clinics of Minnesota |
December 22, 2009 | Not Applicable |
| NCT00945009 | Active Recruiting |
Biological: Dactinomycin Drug: Vincristine Sulfate |
Adult Kidney Wilms Tumor Stage I Kidney Wilms Tumor |
Children's Oncology Group | July 13, 2009 | Phase 3 |
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