actinomycin D

Base Information

• Chemical Name: actinomycin D
• CAS No.: 50-76-0
• Molecular Formula: C62H86N12O16
• Molecular Weight: 1255.44
• Hs Code.: 29419000
• European Community (EC) Number: 200-063-6
• NSC Number: 191297,684906
• UN Number: 2811
• Wikipedia: Dactinomycin
• Wikidata: Q105237811
• Metabolomics Workbench ID: 75133
• ChEMBL ID: CHEMBL427947
• Mol file: 50-76-0.mol

Synonyms:Actinomycin;Actinomycin D;Cosmegen;Cosmegen Lyovac;Dactinomycin;Lyovac Cosmegen;Lyovac, Cosmegen;Lyovac-Cosmegen;LyovacCosmegen;Meractinomycin

Chemical Property of actinomycin D

Chemical Property:

• Appearance/Colour: red crystalline powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 251-253 °C
• Refractive Index: 1.656
• Boiling Point: 1386 °C at 760 mmHg
• Flash Point: 792.1 °C
• PSA: 359.98000
• Density: 1.42 g/cm³
• LogP: 2.37360
• Storage Temp.: 2-8°C
• Solubility.: ethanol, DMSO: Stable in aqueous solutions at 2-8 °C.solu
• Water Solubility.: SOLUBLE
• XLogP3: 3.8
• Hydrogen Bond Donor Count: 5
• Hydrogen Bond Acceptor Count: 18
• Rotatable Bond Count: 8
• Exact Mass: 1254.62847470
• Heavy Atom Count: 90
• Complexity: 3030
• Transport DOT Label: Poison

Purity/Quality:

97% ^*data from raw suppliers

Actinomycin D ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T+
• Hazard Codes: T+
• Statements: 28-61-40-45-26/27/28
• Safety Statements: 53-36/37/39-45-1-36/37-28-22

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• 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
• Recent ClinicalTrials: Evolutionary Therapy for Rhabdomyosarcoma
• Recent EU Clinical Trials: An international prospective umbrella trial for children with atypical teratoid/rhabdoid tumours (ATRT) including A randomized phase III study evaluating the non-inferiority of three courses of high-dose chemotherapy (HDCT) compared to focal radiotherapy as consolidation therapy
• Recent NIPH Clinical Trials: Multi-center clinical trial for Japanese children with bilateral nephroblastoma(RTBL14)
• Description: Actinomycin D (50-76-0) is a cyclopeptide antibiotic and intercalating transcription inhibitor with anti-neoplastic activity. Potent inhibitor of RNA polymerase.1?Induces apoptosis in a variety of cancer cell lines2,3via the intrinsic pathway4.? Upregulates proapoptotic PUMA and downregulates Bcl-2 mRNA in peripheral blood lymphocytes.5
• Uses: Antibiotic substance belonging to the actinomycin complex, produced by several Streptomyces spp. Antineoplastic An antineoplastic antibiotic that inhibits cell proliferation by forming a stable complex with DNA and blocking the movement of RNA polymerase which interferes with DNA-dependent RNA synthesis. Induces apoptosis. Potent antitumor agent. antineoplastic, intercalating agent Actinomycin D is the most studied member of a family of unique bicyclic depsipeptides produced by several Streptomyces species. The depsipeptides are linked by a heterocyclic benzoxazone "anchor" that gives the metabolites a highly distinctive red/orange colour. Actinomycin D exhibits potent antibiotic and antitumour activity via DNA intercalation leading to the inhibition of nucleic acid synthesis. Tumour cell death has been demonstrated to occur by apoptosis.
• Indications: Dactinomycin (actinomycin D, Cosmegen) is one of a family of chromopeptides produced by Streptomyces. It is known to bind noncovalently to double-strand DNA by partial intercalation, inhibiting DNA-directed RNA synthesis. The drug is most toxic to proliferating cells, but it is not specific for any one phase of the cell cycle. Resistance to dactinomycin is caused by decreased ability of tumor cells to take up and retain the drug, and it is associated with cross-resistance to vinca alkaloids, the anthracyclines, and certain other agents (multidrug resistance).
• Therapeutic Function: Cancer chemotherapy
• Clinical Use: Dactinomycin is used in curative combined treatment of Wilms’ tumor, Ewing’s sarcoma, rhabdomyosarcoma, and gestational choriocarcinoma. It is active in testicular tumors, lymphomas, melanomas, and sarcomas, although its use in most of these malignancies has been supplanted by other agents.
• Drug interactions: Potentially hazardous interactions with other drugsAntipsychotics: increased risk of agranulocytosis with clozapine - avoid.Cytotoxics: increased risk of hepatotoxicity with vincristine.Vaccines: risk of generalised infections with live vaccines - avoid.

Technology Process of actinomycin D

There total 15 articles about actinomycin D which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield:

<3-(benzyloxy)-4-methyl-2-nitrobenzoyl>-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine lactone (2478-48-0) → actinomycin D (50-76-0)

Guidance literature:

Multistep reaction; (i) H2, Pd-C, MeOH, (ii) aq. K3, DMF;

DOI:10.1002/cber.19701030819

Reference yield:

<3-(benzyloxy)-4-methyl-2-nitro-benzoyl>-L-threonine (2441-62-5) → actinomycin D (50-76-0)

Guidance literature:

Multi-step reaction with 6 steps

1: HONB/DCC / dimethylformamide / 48 h / -5 °C

2: 89 percent / DMAP/DCC / CH₂Cl₂ / 16 h / 26 °C

3: 1.) 4N HCl, 2.) aq. sodium hydroxide / dioxane / 2 h / 22 °C

4: diisopropylethylamine, BOP-Cl / CH₂Cl₂ / 72 h / 22 °C

5: 94 percent / trifluoromethane-sulfonic acid / CH₂Cl₂ / 0.17 h / 23 °C

6: 1.) H₂; 2.) potassium ferricyanide / 1.) 10percent palladium/charcoal / 1.) methanol, ethylacetate, 3 h; 2.) methanol, 23 deg C, 10 min

With hydrogenchloride; dmap; sodium hydroxide; trifluorormethanesulfonic acid; hydrogen; bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide; (3aR,4R,7S,7aS)-2-hydroxy-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione (N-hydroxy-5-exo-norbornene-2,3-dicarboximide); potassium hexacyanoferrate(III); palladium on activated charcoal; In 1,4-dioxane; dichloromethane; N,N-dimethyl-formamide;

DOI:10.1021/ja00310a065

Reference yield:

<3-(benzyloxy)-4-methyl-2-nitrobenzoyl>-L-threonyl-D-valyl-L-prolyl-sarcosine tert-butyl ester (6041-34-5) → actinomycin D (50-76-0)

Guidance literature:

Multi-step reaction with 5 steps

1: 89 percent / DMAP/DCC / CH₂Cl₂ / 16 h / 26 °C

2: 1.) 4N HCl, 2.) aq. sodium hydroxide / dioxane / 2 h / 22 °C

3: diisopropylethylamine, BOP-Cl / CH₂Cl₂ / 72 h / 22 °C

4: 94 percent / trifluoromethane-sulfonic acid / CH₂Cl₂ / 0.17 h / 23 °C

5: 1.) H₂; 2.) potassium ferricyanide / 1.) 10percent palladium/charcoal / 1.) methanol, ethylacetate, 3 h; 2.) methanol, 23 deg C, 10 min

With hydrogenchloride; dmap; sodium hydroxide; trifluorormethanesulfonic acid; hydrogen; bis-(2-oxo-3-oxazolidinyl)phosphoryl chloride; N-ethyl-N,N-diisopropylamine; dicyclohexyl-carbodiimide; potassium hexacyanoferrate(III); palladium on activated charcoal; In 1,4-dioxane; dichloromethane;

DOI:10.1021/ja00310a065

upstream raw materials:

actinomycin-A5-oic-D acid

<3-(benzyloxy)-4-methyl-2-nitrobenzoyl>-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine lactone

N-(3-benzyloxy-4-methyl-2-nitro-benzoyl)-L_s-threonyl->D-valyl->L-prolyl->N-methyl-glycyl->N-methyl-L-valine benzyl ester

(3-hydroxy-4-methyl-2-nitrobenzoyl)-L-threonyl-D-valyl-L-prolyl-sarcosyl-N-methyl-L-valine lactone

Downstream raw materials:

2-hydroxyactinomycin D

Refernces

• 1、 -. "Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same". . . Retrieved 2010/05/13.
• 2、 -. "Synthetic lipid-a-analogs and uses thereof". . . Retrieved 2009/03/07.