Dactinomycin | Actinomycin D | CAS#50-76-0 | polypeptide antibiotics

MedKoo Cat#: 100220 | Name: Dactinomycin

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Dactinomycin (also known generically as Actinomycin D) is the most significant member of actinomycines, which are a class of polypeptide antibiotics isolated from soil bacteria of the genus Streptomyces. As one of the older chemotherapy drugs, it has been used for many years. Actinomycin D was the first antibiotic shown to have anti-cancer activity. It was first isolated by Selman Waksman and his co-worker H. B. Woodruff in 1940. It was approved by the US FDA on December 10, 1964 and launched by Merck Sharp and Dohme under the trade name Cosmegen.

Chemical Structure

Dactinomycin

CAS#50-76-0

Theoretical Analysis

MedKoo Cat#: 100220

Name: Dactinomycin

CAS#: 50-76-0

Chemical Formula: C62H86N12O16

Exact Mass: 1254.6285

Molecular Weight: 1255.42

Elemental Analysis: C, 59.32; H, 6.90; N, 13.39; O, 20.39

Price and Availability

Size	Price	Availability
1mg	USD 75.00	Ready to ship
5mg	USD 185.00	Ready to ship
10mg	USD 300.00	Ready to ship
25mg	USD 550.00	Ready to ship
50mg	USD 950.00	Ready to ship

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Related CAS #

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Synonym

Abbreviation: DACT; ACTD; actinomycin C1; actinomycin D; actinomycin I1; actinomycin IV; actinomycin X 1; actinomycinthrvalprosarmeval; dactinomycine; meractinomycin; US brand names: Cosmegen; Lyovac.

IUPAC/Chemical Name

2-amino-N1,N9-bis((6S,9R,10S,13R,18aS)-6,13-diisopropyl-2,5,9-trimethyl-1,4,7,11,14-pentaoxohexadecahydro-1H-pyrrolo[2,1-i][1]oxa[4,7,10,13]tetraazacyclohexadecin-10-yl)-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxamide

InChi Key

RJURFGZVJUQBHK-IIXSONLDSA-N

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

SMILES Code

O=C(N[C@@H]1C(N[C@@H](C(N2[C@]([H])(C(N(CC(N([C@H](C(O[C@@H]1C)=O)C(C)C)C)=O)C)=O)CCC2)=O)C(C)C)=O)C3=C(C(C(C)=C4OC5=C(C(C(N[C@@H]([C@@H](C)O6)C(N[C@H](C(C)C)C(N7CCC[C@@]7([H])C(N(C)CC(N(C)[C@@H](C(C)C)C6=O)=O)=O)=O)=O)=O)=CC=C5C)N=C43)=O)N

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

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. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus). Clinical use As chemotherapy: Actinomycin D, marketed under the trade name Dactinomycin, is one of the older chemotherapy drugs, and has been used in therapy for many years. It is a clear, yellow liquid administered intravenously and most commonly used in treatment of a variety of cancers including gestational trophoblastic neoplasia, Wilms' tumor and rhabdomyosarcoma. As an antibiotic: It was the first antibiotic shown to have anti-cancer activity, but is not normally used as such, as it is highly toxic, causing damage to genetic material. Research use: Actinomycin D and its fluorescent derivative, 7-aminoactinomycin D (7-AAD), are used as stains in microscopy and flow cytometry applications. The affinity of these stains/compounds for GC-rich regions of DNA strands makes them excellent markers for DNA. 7-AAD binds to single stranded DNA; therefore it is a useful tool in determining apoptosis and distinguishing between dead cells and live ones. From http://en.wikipedia.org/wiki/Dactinomycin . DRUG DESCRIPTION Dactinomycin is one of the actinomycins, a group of antibiotics produced by various species of Streptomyces. Dactinomycin is the principal component of the mixture of actinomycins produced by Streptomyces parvullus. Unlike other species of Streptomyces, this organism yields an essentially pure substance that contains only traces of similar compounds differing in the amino acid content of the peptide side chains. The empirical formula is C62H86N12O16. COSMEGEN is a sterile, yellow to orange lyophilized powder for injection by the intravenous route or by regional perfusion after reconstitution. Each vial contains 0.5 mg (500 mcg) of dactinomycin and 20.0 mg of mannitol. Mechanism of Action 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 implants. 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.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#TZC50824

QC Data

View QC data: current batch, Lot#TZC50824

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Actinomycin D (Dactinomycin) inhibits DNA repair and rests the cell cycle at G1 phase with IC50 of 0.42 μM and 0.4 nM, respectively.

In vitro activity:

In an extensive screen for p53-independent apoptosis inducers, actinomycin D was identified and shown to induce apoptosis in primary chronic lymphocytic leukemia (CLL) cells derived from high-risk patients including those with aberrations in the p53 pathway, such as a deleted (del17p13) or mutated p53 gene, revealing a novel p53-independent mechanism of action. Both pro-survival genes BCL2 and MCL1 are targeted by actinomycin D. Reference: Leukemia. 2012 Dec;26(12):2508-16. https://www.nature.com/articles/leu2012147

In vivo activity:

Whether the administration of the RNA synthesis inhibitor dactinomycin can prevent retinal photoreceptor cell injury induced by green wavelength of argon laser was tested in SD mice. Intraocular administration of dactinomycin diminished the degeneration induced by argon laser, there were marked differences between the experimental group and the control group, dactinomycin showed to be more effective if administered immediately after exposure and 8 h later, after this time the higher concentration of the drug could not result in higher effect. These data suggest that dactinomycin can inhibit the occurrence of the laser injury, but the time selected for the administration is critical for its efficacy. Reference: Zhonghua Yan Ke Za Zhi. 2000 Jul;36(4):299-301. https://pubmed.ncbi.nlm.nih.gov/11853620/

	Solvent	mg/mL	mM
Solubility
	DMSO	90.7	72.24
	DMF	20.0	15.93
	DMF:PBS (pH 7.2)(1:1)	0.5	0.40

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 1,255.42 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Merkel O, Wacht N, Sifft E, Melchardt T, Hamacher F, Kocher T, Denk U, Hofbauer JP, Egle A, Scheideler M, Schlederer M, Steurer M, Kenner L, Greil R. Actinomycin D induces p53-independent cell death and prolongs survival in high-risk chronic lymphocytic leukemia. Leukemia. 2012 Dec;26(12):2508-16. doi: 10.1038/leu.2012.147. Epub 2012 Jun 1. PMID: 22743622. 2. Liu Y, He S. [The effect of dactinomycin on retinal injury induced by argon laser in mouse]. Zhonghua Yan Ke Za Zhi. 2000 Jul;36(4):299-301. Chinese. PMID: 11853620.

In vitro protocol:

In vivo protocol:

1. Liu Y, He S. [The effect of dactinomycin on retinal injury induced by argon laser in mouse]. Zhonghua Yan Ke Za Zhi. 2000 Jul;36(4):299-301. Chinese. PMID: 11853620.

1: Weaver MS, Navid F, Huppmann A, Meany H, Angiolillo A. Vincristine and Dactinomycin in Infantile Myofibromatosis With a Review of Treatment Options. J Pediatr Hematol Oncol. 2014 Nov 11. [Epub ahead of print] PubMed PMID: 25389917. 2: Walterhouse DO, Pappo AS, Meza JL, Breneman JC, Hayes-Jordan AA, Parham DM, Cripe TP, Anderson JR, Meyer WH, Hawkins DS. Shorter-duration therapy using vincristine, dactinomycin, and lower-dose cyclophosphamide with or without radiotherapy for patients with newly diagnosed low-risk rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol. 2014 Nov 1;32(31):3547-52. doi: 10.1200/JCO.2014.55.6787. Epub 2014 Sep 29. PubMed PMID: 25267746; PubMed Central PMCID: PMC4209105. 3: Raggi D, Giannatempo P, Miceli R, FarÃ¨ E, Piva L, Biasoni D, Catanzaro M, Torelli T, Stagni S, Marongiu M, Gianni AM, Nicolai N, Salvioni R, Necchi A. Etoposide, Methotrexate, and Dactinomycin Alternating With Cyclophosphamide and Vincristine (EMACO) for Male Patients With HCG-expressing, Chemoresistant Germ Cell Tumors. Am J Clin Oncol. 2014 Aug 7. [Epub ahead of print] PubMed PMID: 25089532. 4: Wang T, Feng FZ, Xiang Y, Wan XR, Ren T. Combination chemotherapy regimen with floxuridine, dactinomycin, etoposide, and vincristine as primary treatment for gestational trophoblastic neoplasia. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2014 Jun;36(3):300-4. doi: 10.3881/j.issn.1000-503X.2014.03.013. PubMed PMID: 24997824. 5: Han SN, Amant F, Leunen K, Devi UK, Neven P, Vergote I. EP-EMA regimen (etoposide and cisplatin with etoposide, methotrexate, and dactinomycin) in a series of 18 women with gestational trophoblastic neoplasia. Int J Gynecol Cancer. 2012 Jun;22(5):875-80. doi: 10.1097/IGC.0b013e31824d834d. PubMed PMID: 22635033. 6: Eiriksson L, Wells T, Steed H, Schepansky A, Capstick V, Hoskins P, Pike J, Swenerton K. Combined methotrexate-dactinomycin: an effective therapy for low-risk gestational trophoblastic neoplasia. Gynecol Oncol. 2012 Mar;124(3):553-7. doi: 10.1016/j.ygyno.2011.10.036. Epub 2011 Nov 9. PubMed PMID: 22079360. 7: Lee AC, Goh PY. Dactinomycin-induced Hepatic Sinusoidal Obstruction Syndrome Responding to Treatment with N-acetylcysteine. J Cancer. 2011;2:527-31. Epub 2011 Oct 25. PubMed PMID: 22043237; PubMed Central PMCID: PMC3204401. 8: Rabbani-Chadegani A, Keyvani-Ghamsari S, Zarkar N. Spectroscopic studies of dactinomycin and vinorelbine binding to deoxyribonucleic acid and chromatin. Spectrochim Acta A Mol Biomol Spectrosc. 2011 Dec 15;84(1):62-7. doi: 10.1016/j.saa.2011.08.064. Epub 2011 Sep 6. PubMed PMID: 21981942. 9: Langholz B, Skolnik JM, Barrett JS, Renbarger J, Seibel NL, Zajicek A, Arndt CA. Dactinomycin and vincristine toxicity in the treatment of childhood cancer: a retrospective study from the Children's Oncology Group. Pediatr Blood Cancer. 2011 Aug;57(2):252-7. doi: 10.1002/pbc.22882. Epub 2010 Dec 1. PubMed PMID: 21671362; PubMed Central PMCID: PMC3467305. 10: Raney RB, Walterhouse DO, Meza JL, Andrassy RJ, Breneman JC, Crist WM, Maurer HM, Meyer WH, Parham DM, Anderson JR. Results of the Intergroup Rhabdomyosarcoma Study Group D9602 protocol, using vincristine and dactinomycin with or without cyclophosphamide and radiation therapy, for newly diagnosed patients with low-risk embryonal rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group. J Clin Oncol. 2011 Apr 1;29(10):1312-8. doi: 10.1200/JCO.2010.30.4469. Epub 2011 Feb 28. PubMed PMID: 21357783; PubMed Central PMCID: PMC3083999. 11: Osborne RJ, Filiaci V, Schink JC, Mannel RS, Alvarez Secord A, Kelley JL, Provencher D, Scott Miller D, Covens AL, Lage JM. Phase III trial of weekly methotrexate or pulsed dactinomycin for low-risk gestational trophoblastic neoplasia: a gynecologic oncology group study. J Clin Oncol. 2011 Mar 1;29(7):825-31. doi: 10.1200/JCO.2010.30.4386. Epub 2011 Jan 24. PubMed PMID: 21263100; PubMed Central PMCID: PMC3068058. 12: Feng F, Xiang Y, Wan X, Geng S, Wang T. Salvage combination chemotherapy with floxuridine, dactinomycin, etoposide, and vincristine (FAEV) for patients with relapsed/chemoresistant gestational trophoblastic neoplasia. Ann Oncol. 2011 Jul;22(7):1588-94. doi: 10.1093/annonc/mdq649. Epub 2011 Jan 13. PubMed PMID: 21239399. 13: Kang WD, Kim CH, Cho MK, Kim JW, Cho HY, Kim YH, Choi HS, Kim SM. Serum hCG level and rising world health organization score at second-line chemotherapy (pulse dactinomycin): poor prognostic factors for methotrexate-failed low-risk gestational trophoblastic neoplasia. Int J Gynecol Cancer. 2010 Nov;20(8):1424-8. doi: 10.1111/IGC.0b013e3181f5873e. PubMed PMID: 21051988. 14: Chang JW, Hsieh JJ, Shen YC, Ho E, Chuang CK, Chen YR, Liao SK, Chen JS, Leong SP, Hou MM, Chang NJ, Wang CH. Immunotherapy with dendritic cells pulsed by autologous dactinomycin-induced melanoma apoptotic bodies for patients with malignant melanoma. Melanoma Res. 2009 Oct;19(5):309-15. PubMed PMID: 19750589. 15: Brady MS, Brown K, Patel A, Fisher C, Marx W. Isolated limb infusion with melphalan and dactinomycin for regional melanoma and soft-tissue sarcoma of the extremity: final report of a phase II clinical trial. Melanoma Res. 2009 Apr;19(2):106-11. doi: 10.1097/CMR.0b013e32832985e3. PubMed PMID: 19282789. 16: Fujioka S, Yamashita Y, Kawabe S, Kamegai H, Terai Y, Ohmichi M. A case of a methotrexate-resistant ectopic pregnancy in which dactinomycin was effective as a second-line chemotherapy. Fertil Steril. 2009 Mar;91(3):929.e13-5. doi: 10.1016/j.fertnstert.2008.10.003. Epub 2009 Jan 10. PubMed PMID: 19135660. 17: Taran A, Ignatov A, Smith B, Bischoff J, Costa SD. Methotrexate monotherapy for high-risk gestational trophoblastic neoplasia after therapy with etoposide, methotrexate, and dactinomycin: a case report. Am J Obstet Gynecol. 2008 Nov;199(5):e6-8. doi: 10.1016/j.ajog.2008.07.045. PubMed PMID: 18984073. 18: Meany HJ, Seibel NL, Sun J, Finklestein JZ, Sato J, Kelleher J, Sondel P, Reaman G. Phase 2 trial of recombinant tumor necrosis factor-alpha in combination with dactinomycin in children with recurrent Wilms tumor. J Immunother. 2008 Sep;31(7):679-83. doi: 10.1097/CJI.0b013e3181826d72. PubMed PMID: 18600176; PubMed Central PMCID: PMC2677078. 19: AbrÃ£o RA, de Andrade JM, Tiezzi DG, Marana HR, Candido dos Reis FJ, Clagnan WS. Treatment for low-risk gestational trophoblastic disease: comparison of single-agent methotrexate, dactinomycin and combination regimens. Gynecol Oncol. 2008 Jan;108(1):149-53. Epub 2007 Oct 10. PubMed PMID: 17931696. 20: Markasz L, Kis LL, Stuber G, Flaberg E, Otvos R, Eksborg S, Skribek H, Olah E, Szekely L. Hodgkin-lymphoma-derived cells show high sensitivity to dactinomycin and paclitaxel. Leuk Lymphoma. 2007 Sep;48(9):1835-45. PubMed PMID: 17786721.