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1. Actinomycin
2. Actinomycin D
3. Cosmegen
4. Cosmegen Lyovac
5. Lyovac Cosmegen
6. Lyovac, Cosmegen
7. Lyovac-cosmegen
8. Lyovaccosmegen
9. Meractinomycin
1. Actinomycin D
2. Actinomycin C1
3. Actinomycin Iv
4. Cosmegen
5. Meractinomycin
6. 50-76-0
7. Actinomycin I1
8. Dactinomycinum
9. Dilactone Actinomycin D Acid
10. Actd
11. Actinomycin X1
12. Oncostatin K
13. Actinomycin-d
14. Act D
15. Nci-c04682
16. Dactinomycine [inn-french]
17. Dactinomycinum [inn-latin]
18. Dactinomicina [inn-spanish]
19. Lyovac Cosmegen
20. Gnf-pf-2290
21. Dactinomycin D
22. Chounghwamycin B
23. Actinomycin 7
24. Actinomycin Aiv
25. Actinomycin I
26. Mls001424196
27. 1cc1jfe158
28. Chebi:27666
29. Actinomycin X 1
30. Actinomycin A Iv
31. Acto-d
32. Nsc-3053
33. Actinomycin C(sub1)
34. Dilactone Actinomycindioic D Acid
35. Ncgc00161622-02
36. Actinomycin I(sub 1)
37. Smr000469227
38. Dsstox_cid_31
39. Actinomycin 11 Cosmegen
40. Cosmegen Lyovac
41. Lyovac-cosmegen
42. Ccris 9
43. Dsstox_rid_75330
44. Dsstox_gsid_20031
45. 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
46. Hsdb 3220
47. Dactinomicina
48. Dactinomycine
49. Actinomycindioic D Acid, Dilactone
50. Antibiotic From Streptomyces Parvullus
51. Actinomycin-(threo-val-pro-sar-meval)
52. Cas-50-76-0
53. Act [antibiotic]
54. X 97
55. 2-amino-n,n'-bis(hexadecahydro-2,5,9-trimethyl-6,13-bis(1-methylethyl)-1,4,7,11,14-pentaoxo-1h-pyrrolo(2,1-i)(1,4,7,10,13)oxatetra-azacyclohexadecin-10-yl)-4,6-dimethyl-3-oxo-3h-phenoxazine-1,9-dicarboxamide
56. Mfcd00005033
57. Ad (van)
58. Gnf-pf-1977
59. Nsc3053
60. Unii-1cc1jfe158
61. Dtxsid9020031
62. Glycopeptide, 4a
63. 2-amino-4,6-dimethyl-3-oxo-n,n'-bis[(6s,9r,10s,13r,18as)-2,5,9-trimethyl-6,13-bis(1-methylethyl)-1,4,7,11,14-pentaoxohexadecahydro-1h-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-3h-phenoxazine-1,9-dicarboxamide
64. Nsc 3053
65. Dactinomycin [usan:usp:inn:ban]
66. Einecs 200-063-6
67. Ai3-26374
68. Dactinomycin [mi]
69. Dactinomycin [inn]
70. Upcmld-dp055
71. Dactinomycin [hsdb]
72. Dactinomycin [usan]
73. Schembl3844
74. Actinomycin D [jan]
75. Chembl1554
76. Dactinomycin [vandf]
77. Actinomycin D [iarc]
78. Dactinomycin [mart.]
79. Dactinomycin [usp-rs]
80. Dactinomycin [who-dd]
81. Dactinomycin [who-ip]
82. Cid_457193
83. Actinomycin D [who-ip]
84. Upcmld-dp055:001
85. Upcmld-dp055:002
86. Bdbm43866
87. Dactinomycin [orange Book]
88. Hms2052o17
89. Dactinomycin [usp Monograph]
90. Tox21_111997
91. Tox21_202482
92. Bdbm50089528
93. S8964
94. Dactinomycinum [who-ip Latin]
95. Akos030228553
96. Tox21_111997_1
97. Ccg-101134
98. Db00970
99. Nc00384
100. Ncgc00090796-01
101. Ncgc00161622-01
102. Ncgc00260031-01
103. Ncgc00271789-02
104. 3h-phenoxazine-1,9-dicarboxamide, 2-amino-n,n'-bis(hexadecahydro-2,5,9-trimethyl-6,13-bis(1-methylethyl)-1,4,7,11,14-pentaoxo-1h-pyrrolo(2,1-i)(1,4,7,10,13)oxatetra-azacyclohexadecin-10-yl)-4,6-dimethyl-3-oxo-
105. Bp-25384
106. Specific Stereoisomer Of N,n'-((2-amino-4,6-dimethyl-3-oxo-3h-phenoxazine-1,9-diyl)-bis(carbonylimino(2-hydroxypropylidene)carbonyliminoisobutylidenecarbonyl-1,2-pyrrolidinediylcarbonyl(methylimino)methylenecarbonyl))bis(n-methyl-l-valine) Dilactone
107. Stereoisomer Of N,n'-((2-amino-4,6-dimethyl-3-oxo-3h-phenoxazine-1,9-diyl)bis(carbonylimino(2-(1-hydroxyethyl)-1-oxo-2,1-ethanediyl)imino(2-(1-methylethyl)-1-oxo-2,1-ethanediyl)-1,2-pyrrolidinediylcarbonyl(methylimino) (1-oxo-2,1-ethanediyl)))bis(n-methyl-l-valine)di-xi-lactone
108. Ab00514445-05
109. 050a760
110. Q186127
111. Sr-01000763161
112. Sr-01000763161-4
113. Actinomycin D, From Streptomyces Sp., >=95% (hplc)
114. Actinomycin D, From Streptomyces Sp., ~98% (hplc)
115. Brd-k70578146-001-01-8
116. Brd-k70578146-001-04-2
117. Dactinomycin, United States Pharmacopeia (usp) Reference Standard
118. Actinomycin D, For Fluorescence, >=90% (hplc), From Streptomyces Sp.
119. Actinomycin D, From Streptomyces Sp., Suitable For Cell Culture, >=95%
120. 1-n,9-n-bis[(6s,9r,10s,13r,18as)-2,5,9-trimethyl-1,4,7,11,14-pentaoxo-6,13-bis(propan-2-yl)-hexadecahydro-1h-pyrrolo[2,1-i]1-oxa-4,7,10,13-tetraazacyclohexadecan-10-yl]-2-amino-4,6-dimethyl-3-oxo-3h-phenoxazine-1,9-dicarboxamide
121. 2-amino-4,6-dimethyl-3-oxo-1-n,9-n-bis-[(18as)-10c,14,17-trimethyl-5,8,12,15,18-pentaoxo-6c,13t-di(propan-2-yl)-18ar-hexadecahydro-1h-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-9c-yl]-3h-phenoxazine-1,9-dicarboxamide
122. 2-amino-4,6-dimethyl-3-oxo-n1,n9-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
123. 2-amino-n,n''''''''-bis[(3r,6s,7r,10s,16s)-3,10-diisopropyl-2,5,9,12,15-pentaketo-7,11,14-trimethyl-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]-3-keto-4,6-dimethyl-phenoxazine-1,9-dicarboxamide
124. 2-amino-n,n''''-bis[(3r,6s,7r,10s,16s)-3,10-diisopropyl-2,5,9,12,15-pentaketo-7,11,14-trimethyl-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]-3-keto-4,6-dimethyl-phenoxazine-1,9-dicarboxamide
125. 2-amino-n,n''-bis[(3r,6s,7r,10s,16s)-3,10-diisopropyl-2,5,9,12,15-pentaketo-7,11,14-trimethyl-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]-3-keto-4,6-dimethyl-phenoxazine-1,9-dicarboxamide
126. 2-amino-n1,n9-bis[(3r,6s,7r,10s,16s)-3,10-diisopropyl-7,11,14-trimethyl-2,5,9,12,15-pentaoxo-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]-4,6-dimethyl-3-oxo-phenoxazine-1,9-dicarboxamide
127. 2-azanyl-4,6-dimethyl-3-oxidanylidene-n1,n9-bis[(3r,6s,7r,10s,16s)-7,11,14-trimethyl-2,5,9,12,15-pentakis(oxidanylidene)-3,10-di(propan-2-yl)-8-oxa-1,4,11,14-tetrazabicyclo[14.3.0]nonadecan-6-yl]phenoxazine-1,9-dicarboxamide
128. 3h-phenoxazine-1,9-dicarboxamide, 2-amino-n,n'-bis(hexadecahydro-6,13-diisopropyl-2,5,9-trimethyl-1,4,7,11,14-pentaoxo-1h-pyrrolo(2,1-i)(1,4,7,10,13)oxatetraazacyclohexadecin-10-yl)-4,6-dimethyl-3-oxo-
129. N,n'-((2-amino-4,6-dimethyl-3-oxo-3h-phenoxazine-1,9-diyl)-bis(carbonylimino(2-hydroxypropylidene)carbonyliminoisobutylidenecarbonyl-1,2-pyrrolidinediylcarbonyl(methylimino)methylenecarbonyl))bis(n-methyl-l-valine) Dilactone
| Molecular Weight | 1255.4 g/mol |
|---|---|
| Molecular Formula | C62H86N12O16 |
| XLogP3 | 3.8 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 18 |
| Rotatable Bond Count | 8 |
| Exact Mass | 1254.62847470 g/mol |
| Monoisotopic Mass | 1254.62847470 g/mol |
| Topological Polar Surface Area | 356 Ų |
| Heavy Atom Count | 90 |
| Formal Charge | 0 |
| Complexity | 3030 |
| Isotope Atom Count | 0 |
| Defined Atom Stereocenter Count | 10 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Covalently Bonded Unit Count | 1 |
| 1 of 4 | |
|---|---|
| Drug Name | Cosmegen |
| PubMed Health | Dactinomycin (Injection) |
| Drug Classes | Antibiotic |
| Drug Label | 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 Streptomyc... |
| Active Ingredient | Dactinomycin |
| Dosage Form | Injectable |
| Route | Injection |
| Strength | 0.5mg/vial |
| Market Status | Prescription |
| Company | Recordati Rare |
| 2 of 4 | |
|---|---|
| Drug Name | Dactinomycin |
| PubMed Health | Dactinomycin (Injection) |
| Drug Classes | Antibiotic |
| Drug Label | 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 Streptomyc... |
| Active Ingredient | Dactinomycin |
| Dosage Form | Injectable |
| Route | Injection |
| Strength | 0.5mg/vial |
| Market Status | Prescription |
| Company | Luitpold; Eurohlth Intl |
| 3 of 4 | |
|---|---|
| Drug Name | Cosmegen |
| PubMed Health | Dactinomycin (Injection) |
| Drug Classes | Antibiotic |
| Drug Label | 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 Streptomyc... |
| Active Ingredient | Dactinomycin |
| Dosage Form | Injectable |
| Route | Injection |
| Strength | 0.5mg/vial |
| Market Status | Prescription |
| Company | Recordati Rare |
| 4 of 4 | |
|---|---|
| Drug Name | Dactinomycin |
| PubMed Health | Dactinomycin (Injection) |
| Drug Classes | Antibiotic |
| Drug Label | 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 Streptomyc... |
| Active Ingredient | Dactinomycin |
| Dosage Form | Injectable |
| Route | Injection |
| Strength | 0.5mg/vial |
| Market Status | Prescription |
| Company | Luitpold; Eurohlth Intl |
Antineoplastic; Anti-Bacterial Agents; Nucleic Acid Synthesis Inhibitors; Protein Synthesis Inhibitors
National Library of Medicine's Medical Subject Headings online file (MeSH, 2009)
Dactinomycin, as part of a combination chemotherapy and/or multi-modality treatment regimen, is indicated for the treatment of Wilms' tumor, childhood rhabdomyosarcoma, Ewing's sarcoma and metastatic, nonseminomatous testicular cancer. /Included in US Product label/
US Natl Inst Health; DailyMed. Current Medication Information for COSMEGEN (dactinomycin) injection, powder, lyophilized, for solution (March 2009). Available from, as of October 14, 2009 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10007
Dactinomycin is indicated as a single agent, or as part of a combination chemotherapy regimen, for the treatment of gestational trophoblastic neoplasia. /Included in US Product label/
US Natl Inst Health; DailyMed. Current Medication Information for COSMEGEN (dactinomycin) injection, powder, lyophilized, for solution (March 2009). Available from, as of October 14, 2009 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10007
Dactinomycin, as a component of regional perfusion, is indicated for the palliative and/or adjunctive treatment of locally recurrent or locoregional solid malignancies. /Included in US Product label/
US Natl Inst Health; DailyMed. Current Medication Information for COSMEGEN (dactinomycin) injection, powder, lyophilized, for solution (March 2009). Available from, as of October 14, 2009 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10007
For more Therapeutic Uses (Complete) data for DACTINOMYCIN (7 total), please visit the HSDB record page.
/BOXED WARNING/ COSMEGEN (Dactinomycin for Injection) should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.
US Natl Inst Health; DailyMed. Current Medication Information for COSMEGEN (dactinomycin) injection, powder, lyophilized, for solution (Updated: February 2013). Available from, as of April 24, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9914e793-a49c-eb00-1ab7-f606c786fe25
/BOXED WARNING/ This drug is HIGHLY TOXIC and both powder and solution must be handled and administered with care. Inhalation of dust or vapors and contact with skin or mucous membranes, especially those of the eyes, must be avoided. Avoid exposure during pregnancy. Due to the toxic properties of dactinomycin (eg, corrosivity, carcinogenicity, mutagenicity, teratogenicity), special handling procedures should be reviewed prior to handling and followed diligently. Dactinomycin is extremely corrosive to soft tissue. If extravasation occurs during intravenous use, severe damage to soft tissues will occur. In at least one instance, this has led to contracture of the arms.
US Natl Inst Health; DailyMed. Current Medication Information for COSMEGEN (dactinomycin) injection, powder, lyophilized, for solution (Updated: February 2013). Available from, as of April 24, 2015: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9914e793-a49c-eb00-1ab7-f606c786fe25
COSMEGEN is a toxic drug and very careful and frequent observation of the patient for adverse reactions is necessary. These reactions may involve any tissue of the body, most commonly the hematopoietic system resulting in myelosuppression. As such, live virus vaccines should not be administered during therapy with COSMEGEN. The possibility of an anaphylactoid reaction should be borne in mind.
US Natl Inst Health; DailyMed. Current Medication Information for COSMEGEN (dactinomycin) injection, powder, lyophilized, for solution (March 2009). Available from, as of October 14, 2009 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10007
Pt may ... become more susceptible to infections due to suppression of normal immune mechanisms. If dactinomycin is given at or about time of infection with chickenpox, severe generalized disease, which is sometimes fatal, may occur.
American Medical Association, AMA Department of Drugs, AMA Drug Evaluations. 3rd ed. Littleton, Massachusetts: PSG Publishing Co., Inc., 1977., p. 1130
For more Drug Warnings (Complete) data for DACTINOMYCIN (24 total), please visit the HSDB record page.
For the treatment of Wilms' tumor, childhood rhabdomyosarcoma, Ewing's sarcoma and metastatic, nonseminomatous testicular cancer as part of a combination chemotherapy and/or multi-modality treatment regimen
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.
Antibiotics, Antineoplastic
Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms. (See all compounds classified as Antibiotics, Antineoplastic.)
Nucleic Acid Synthesis Inhibitors
Compounds that inhibit cell production of DNA or RNA. (See all compounds classified as Nucleic Acid Synthesis Inhibitors.)
Protein Synthesis Inhibitors
Compounds which inhibit the synthesis of proteins. They are usually ANTI-BACTERIAL AGENTS or toxins. Mechanism of the action of inhibition includes the interruption of peptide-chain elongation, the blocking the A site of ribosomes, the misreading of the genetic code or the prevention of the attachment of oligosaccharide side chains to glycoproteins. (See all compounds classified as Protein Synthesis Inhibitors.)
Anti-Bacterial Agents
Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)
L - Antineoplastic and immunomodulating agents
L01 - Antineoplastic agents
L01D - Cytotoxic antibiotics and related substances
L01DA - Actinomycines
L01DA01 - Dactinomycin
Absorption
poorly absorbed from gastrointestinal tract
Dactinomycin is poorly absorbed from the GI tract. The drug is extremely irritating to tissues and, therefore, must be administered iv.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1025
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.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1025
Plasma protein binding /of dactinomycin/ is 5%.
Dart, R.C. (ed). Medical Toxicology. Third Edition, Lippincott Williams & Wilkins. Philadelphia, PA. 2004., p. 494
Dactinomycin apparently crosses the placenta. It is not known if dactinomycin is distributed into milk.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1025
For more Absorption, Distribution and Excretion (Complete) data for DACTINOMYCIN (6 total), please visit the HSDB record page.
hepatic
Dactinomycin appears to be only slightly metabolized; small amounts of monolactones of the drug have been detected in the urine.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1025
36 hours
The terminal plasma half-life for radioactivity was approximately 36 hours.
US Natl Inst Health; DailyMed. Current Medication Information for COSMEGEN (dactinomycin) injection, powder, lyophilized, for solution (March 2009). Available from, as of October 14, 2009 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10007
The terminal elimination half life of actinomycin D is 36 to 48 hours.
Dart, R.C. (ed). Medical Toxicology. Third Edition, Lippincott Williams & Wilkins. Philadelphia, PA. 2004., p. 494
Good evidence exists that this drug bind strongly, but reversibly, to DNA, interfering with synthesis of RNA (prevention of RNA polymerase elongation) and, consequently, with protein synthesis.
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
Hardman, J.G., L.E. Limbird, P.B., A.G. Gilman. Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th ed. New York, NY: McGraw-Hill, 2006., p. 1357
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.
American Society of Health System Pharmacists; AHFS Drug Information 2009. Bethesda, MD. (2009), p. 1025
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.
US Natl Inst Health; DailyMed. Current Medication Information for COSMEGEN (dactinomycin) injection, powder, lyophilized, for solution (March 2009). Available from, as of October 14, 2009 https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=10007
Dactinomycin acts by forming stable complexes with double-helical DNA that inhibit DNA-directed RNA synthesis (interfere with RNA polymerase) more than DNA synthesis. The drug is cell-cycle active.
Booth, N.H., L.E. McDonald (eds.). Veterinary Pharmacology and Therapeutics. 5th ed. Ames, Iowa: Iowa State University Press, 1982., p. 793
The effect of dactinomycin on cellular respiration and accompanying ATP formation was investigated in Jurkat and HL-60 cells. Cellular mitochondrial oxygen consumption (measured by a homemade phosphorescence analyzer) and ATP content (measured by the luciferin-luciferase bioluminescence system) were determined as functions of time t during continuous exposure to the drug. The rate of respiration, k, was the negative of the slope of [O2] versus t. Oxygen consumption and ATP content were diminished by cyanide, confirming that both processes involved oxidations in the mitochondrial respiratory chain. In the presence of dactinomycin, k decreased gradually with t, the decrease being more pronounced at higher drug concentrations. Cellular ATP remained constant for 5 h in untreated cells, but in the presence of 20 microM dactinomycin it decreased gradually (to one-tenth the value at 5 h for untreated cells). The drug-induced inhibition of respiration and decrease in ATP were blocked by the pancaspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethyl ketone (zVAD-fmk). A rapid but temporary decrease in cellular ATP observed on the addition of zVAD-fmk was shown to be due to DMSO (added with zVAD-fmk). The effect of dactinomycin on respiration differed from that of doxorubicin. Plots of [O2] versus t were curved for dactinomycin so that k decreased gradually with t. The corresponding plots for doxorubicin were well fit by two straight lines; so k was constant for approximately 150 min, at which time k decreased, remaining constant at a lower level thereafter. The results for cells treated with mixtures of the two drugs indicated that the drugs acted synergistically. These results show the onset and severity of mitochondrial dysfunction in cells undergoing apoptosis induced by dactinomycin.
PMID:17140264 Tao Z et al; Mol Pharm 3 (6): 762-72 (2006).
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RX/OTC/DISCN : Class H
Dosage Form : Dactinomycin 0.5Mg 1 Unit Parent...
Dosage Strength : 1 vial 0.5 mg Groun
Price Per Pack (Euro) : 96.82
Published in :
Country : Italy
RX/OTC/DISCN : Class H
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