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Dactinomycin

January 01, 1970

Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a number of types of cancer.[2] This includes Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma, trophoblastic neoplasm, testicular cancer, and certain types of ovarian cancer.[2] It is given by injection into a vein.[2]

Dactinomycin
Clinical data
Trade namesCosmegen
Other namesActinomycin D
2-Amino- 4,6-dimethyl- 3-oxo- 3H-phenoxazine- 1,9-dicarboxylic acid bis- [(5,12-diisopropyl- 9,13,16-trimethyl- 4,7,11,14,17-pentaoxo- hexadecahydro- 10-oxa- 3a,6,13,16-tetraaza- cyclopentacyclohexadecen- 8-yl)- amide]
AHFS/Drugs.comMonograph
MedlinePlusa682224
Pregnancy
category
  • AU: D
Routes of
administration		IV
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding5%
Metabolismhepatic
Elimination half-life36 hours
ExcretionBile[1]
Identifiers
  • 2-Amino-N,N′- bis[(6S,9R,10S,13R,18aS)-6,13-diisopropyl-2,5,9-trimethyl-1,4,7,11,14-pentaoxohexadecahydro-1H-pyrrolo[2,1-i][1,4,7,10,13]oxatetraazacyclohexadecin-10-yl]-4,6-dimethyl-3-oxo-3H-phenoxazine-1,9-dicarboxamide
CAS Number
  • 50-76-0 Y
PubChem CID
  • 2019
DrugBank
  • DB00970 N
ChemSpider
  • 10482167 Y
UNII
  • 1CC1JFE158
KEGG
  • C06770 N
ChEBI
  • CHEBI:27666 Y
ChEMBL
  • ChEMBL1554 Y
NIAID ChemDB
  • 009885
CompTox Dashboard (EPA)
  • DTXSID9020031
ECHA InfoCard100.000.058
Chemical and physical data
FormulaC62H86N12O16
Molar mass1255.438 g·mol−1
3D model (JSmol)
  • Interactive image
  • Cc1c2oc3c(C)ccc(C(O)=N[C@@H]4C(O)=N[C@H](C(C)C)C(=O)N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)c3nc-2c(C(O)=N[C@@H]2C(O)=N[C@H](C(C)C)C(=O)N3CCC[C@H]3C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]2C)c(N)c1=O
  • 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 Y
  • Key:RJURFGZVJUQBHK-IIXSONLDSA-N Y
 NY (what is this?)  (verify)

Most people develop side effects.[2] Common side effects include bone marrow suppression, vomiting, mouth ulcers, hair loss, liver problems, infections, and muscle pains.[2] Other serious side effects include future cancers, allergic reactions, and tissue death if extravasation occurs.[2] Use in pregnancy may harm the baby.[2] Dactinomycin is in the cytotoxic antibiotic family of medications.[3] It is believed to work by blocking the creation of RNA.[2]

Dactinomycin was approved for medical use in the United States in 1964.[2] It is on the 2023 World Health Organization's List of Essential Medicines.[4]

Medical use edit

Actinomycin is a clear, yellowish liquid administered intravenously and most commonly used in treatment of a variety of cancers, including:

Sometimes it will be combined with other drugs in chemotherapy regimens, like the VAC regimen (with vincristine and cyclophosphamide) for treating rhabdomyosarcoma and Ewing's sarcoma.[10]

It is also used as a radiosensitizer in adjunct to radiotherapies,[11] since it can increase the radiosensitivity of tumor cells by inhibiting repair of sublethal radiation damage and delay the onset of the compensatory hyperplasia that occurs following irradiation.[12]

Side effects edit

Common adverse drug reaction includes bone marrow suppression, fatigue, hair loss, mouth ulcer, loss of appetite and diarrhea. Actinomycin is a vesicant, if extravasation occurs.

Mechanism edit

In cell biology, actinomycin D is shown to have the ability to inhibit transcription. Actinomycin D does this by binding DNA at the transcription initiation complex and preventing elongation of RNA chain by RNA polymerase.[13]

History edit

Actinomycin D was the first antibiotic shown to have anti-cancer activity.[14] It was first isolated by Selman Waksman and his co-worker H. Boyd Woodruff in 1940,[15] using fermentation products from Streptomyces.[16] It was approved by the U.S. Food and Drug Administration (FDA) on December 10, 1964,[17] and launched by Merck Sharp and Dohme under the trade name Cosmegen.

Research use edit

Because actinomycin can bind DNA duplexes, it can also interfere with DNA replication, although other chemicals such as hydroxyurea are better suited for use in the laboratory as inhibitors of DNA synthesis.

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.[18]

Biosynthesis edit

Actinomycin D is composed of a central phenoxazinone chromophore tethered to two identical cyclic peptides and was first structurally characterized by Nuclear Magnetic Resonance (NMR) analysis in 1982.[19] The biosynthesis of Actinomycin D has been under investigation since its discovery; early fermentation feeding experiments revealed the roles of both tryptophan and D-glutamate as precursor substrates,[20][19] and strain mutagenesis experiments demonstrated that a phenoxazinone synthase enzyme might be responsible for coupling of two moieties of 4-methyl-3-hydroxyanthranilic acid (4-MHA) into the final phenoxazinone structure.[21] The 4-MHA substrate was shown to be produced from tryptophan through the action of enzymes such as tryptophan dioxygenase, kynurenine formamidase, kynurenine hydroxylase, hydroxykynurenase, and methyltransferase.[22][23]

Early experiments elucidated the presence of non-ribosomal peptide synthetases,[24][25][26][27] and subsequent purification and heterologous expression experiments[24][25][28][29] showed the acmD and acmA genes to be responsible for activation of the 4-MHA, which then undergoes chain elongation through the action of the acmB and acmC genes. In total, the NRPS assembly line is composed of twenty-two modules, including two each of epimerase and methylase domains.[30][23] Recent sequencing of the actinomycin D gene cluster in Streptomyces chrysomallus showed that the four NRPS genes were surrounded on both sides by the two clusters of the genes involved in the well-studied kynurenine pathway and responsible for the production of 4-MHA from tryptophan, with nine paralogs identified between the two clusters.[23]

 
Biosynthetic scheme of actinomycin D demonstrating the conversion of tryptophan to 4-MHA and the subsequent elongation by nonribosomal peptide synthetase assembly line genes. Figure modified from Keller et al., 2010.[23]

References edit

  1. ^ Kwok KK, Vincent EC, Gibson JN (2017). Pharmacology and Therapeutics for Dentistry. Mosby. pp. 530–562. doi:10.1016/B978-0-323-39307-2.00036-9.
  2. ^ a b c d e f g h i "Dactinomycin". The American Society of Health-System Pharmacists. from the original on 11 September 2017. Retrieved 8 December 2016.
  3. ^ British national formulary : BNF 69 (69 ed.). British Medical Association. 2015. p. 582. ISBN 9780857111562.
  4. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
  5. ^ Turan T, Karacay O, Tulunay G, Boran N, Koc S, Bozok S, Kose MF (2006). "Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia". International Journal of Gynecological Cancer. 16 (3): 1432–1438. doi:10.1111/j.1525-1438.2006.00606.x. PMID 16803542. S2CID 32560653.
  6. ^ D'Angio GJ, Evans A, Breslow N, Beckwith B, Bishop H, Farewell V, et al. (May 1981). "The treatment of Wilms' tumor: results of the Second National Wilms' Tumor Study". Cancer. 47 (9): 2302–2311. doi:10.1002/1097-0142(19810501)47:9<2302::aid-cncr2820470933>3.0.co;2-k. PMID 6164480.
  7. ^ Khatua S, Nair CN, Ghosh K (November 2004). "Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues". Journal of Pediatric Hematology/Oncology. 26 (11): 777–779. doi:10.1097/00043426-200411000-00020. PMID 15543019.
  8. ^ Jaffe N, Paed D, Traggis D, Salian S, Cassady JR (November 1976). "Improved outlook for Ewing's sarcoma with combination chemotherapy (vincristine, actinomycin D and cyclophosphamide) and radiation therapy". Cancer. 38 (5): 1925–1930. doi:10.1002/1097-0142(197611)38:5<1925::AID-CNCR2820380510>3.0.CO;2-J. PMID 991106.
  9. ^ Uberti EM, Fajardo M, Ferreira SV, Pereira MV, Seger RC, Moreira MA, et al. (December 2009). "Reproductive outcome after discharge of patients with high-risk hydatidiform mole with or without use of one bolus dose of actinomycin D, as prophylactic chemotherapy, during the uterine evacuation of molar pregnancy". Gynecologic Oncology. 115 (3): 476–481. doi:10.1016/j.ygyno.2009.09.012. PMID 19818481.
  10. ^ Arndt CA, Stoner JA, Hawkins DS, Rodeberg DA, Hayes-Jordan AA, Paidas CN, et al. (2009). "Vincristine, Actinomycin, and Cyclophosphamide Compared With Vincristine, Actinomycin, and Cyclophosphamide Alternating With Vincristine, Topotecan, and Cyclophosphamide for Intermediate-Risk Rhabdomyosarcoma: Children's Oncology Group Study D9803". J Clin Oncol. 27 (31): 5182–5188. doi:10.1200/JCO.2009.22.3768. PMC 2773476. PMID 19770373.
  11. ^ Matthews NH, Moustafa F, Kaskas NM, Robinson-Bostom L, Pappas-Taffer L (2020). "41 - Dermatologic Toxicities of Anticancer Therapy". Abeloff's Clinical Oncology. Elsevier. pp. 621–648. doi:10.1016/B978-0-323-47674-4.00041-4. ISBN 9780323476744. S2CID 198317393.
  12. ^ Hagemann RF, Concannon JP (April 1973). "Mechanism of intestinal radiosensitization by actinomycin D". The British Journal of Radiology. 46 (544): 302–308. doi:10.1259/0007-1285-46-544-302. PMID 4720744.
  13. ^ Sobell HM (August 1985). "Actinomycin and DNA transcription". Proceedings of the National Academy of Sciences of the United States of America. 82 (16): 5328–5331. Bibcode:1985PNAS...82.5328S. doi:10.1073/pnas.82.16.5328. PMC 390561. PMID 2410919.
  14. ^ Hollstein U (1974). "Actinomycin. Chemistry and mechanism of action". Chemical Reviews. 74 (6): 625–652. doi:10.1021/cr60292a002.
  15. ^ Waksman SA, Woodruff HB (1940). "Bacteriostatic and bacteriocidal substances produced by soil actinomycetes". Proceedings of the Society for Experimental Biology and Medicine. 45: 609–614. doi:10.3181/00379727-45-11768. S2CID 84774334.
  16. ^ "Dactinomycin". LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. National Institute of Diabetes and Digestive and Kidney Diseases. 2012. PMID 31644085.
  17. ^ "Drugs@FDA: Dactinomycin". FDA. Retrieved 2023-10-15.
  18. ^ Toba K, Koike T, Watanabe K, Fuse I, Takahashi M, Hashimoto S, et al. (January 2000). "Cell kinetic study of normal human bone marrow hematopoiesis and acute leukemia using 7AAD/PY". European Journal of Haematology. 64 (1): 10–21. doi:10.1034/j.1600-0609.2000.09005.x. PMID 10680701. S2CID 41065740.
  19. ^ a b Shafer RH, Formica JV, Delfini C, Brown SC, Mirau PA (December 1982). "Biosynthesis and characterization of [15N]actinomycin D and conformational analysis by nitrogen-15 nuclear magnetic resonance". Biochemistry. 21 (25): 6496–6503. doi:10.1021/bi00268a027. PMID 6129895.
  20. ^ Sivak A, Katz E (July 1962). "Biosynthesis of the actinomycin chromophore. Influence of alpha-, 4-, 5-, and 6-methyl-DL-tryptophan on actinomycin synthesis". Biochimica et Biophysica Acta. 62 (1): 80–90. doi:10.1016/0006-3002(62)90493-6. PMID 13913519.
  21. ^ Troost T, Katz E (March 1979). "Phenoxazinone biosynthesis: accumulation of a precursor, 4-methyl-3-hydroxyanthranilic acid, by mutants of Streptomyces parvulus". Journal of General Microbiology. 111 (1): 121–132. doi:10.1099/00221287-111-1-121. PMID 458423.
  22. ^ Jones GH (December 1987). "Actinomycin synthesis in Streptomyces antibioticus: enzymatic conversion of 3-hydroxyanthranilic acid to 4-methyl-3-hydroxyanthranilic acid". Journal of Bacteriology. 169 (12): 5575–5578. doi:10.1128/jb.169.12.5575-5578.1987. PMC 213988. PMID 2445729.
  23. ^ a b c d Keller U, Lang M, Crnovcic I, Pfennig F, Schauwecker F (May 2010). "The actinomycin biosynthetic gene cluster of Streptomyces chrysomallus: a genetic hall of mirrors for synthesis of a molecule with mirror symmetry". Journal of Bacteriology. 192 (10): 2583–2595. doi:10.1128/JB.01526-09. PMC 2863554. PMID 20304989.
  24. ^ a b Schauwecker F, Pfennig F, Grammel N, Keller U (April 2000). "Construction and in vitro analysis of a new bi-modular polypeptide synthetase for synthesis of N-methylated acyl peptides". Chemistry & Biology. 7 (4): 287–297. doi:10.1016/s1074-5521(00)00103-4. PMID 10780924.
  25. ^ a b Schauwecker F, Pfennig F, Schröder W, Keller U (May 1998). "Molecular cloning of the actinomycin synthetase gene cluster from Streptomyces chrysomallus and functional heterologous expression of the gene encoding actinomycin synthetase II". Journal of Bacteriology. 180 (9): 2468–2474. doi:10.1128/jb.180.9.2468-2474.1998. PMC 107190. PMID 9573200.
  26. ^ Stindl A, Keller U (May 1993). "The initiation of peptide formation in the biosynthesis of actinomycin". The Journal of Biological Chemistry. 268 (14): 10612–10620. doi:10.1016/S0021-9258(18)82242-6. PMID 7683683.
  27. ^ Stindl A, Keller U (August 1994). "Epimerization of the D-valine portion in the biosynthesis of actinomycin D". Biochemistry. 33 (31): 9358–9364. doi:10.1021/bi00197a041. PMID 8049237.
  28. ^ Keller U (April 1987). "Actinomycin synthetases. Multifunctional enzymes responsible for the synthesis of the peptide chains of actinomycin". The Journal of Biological Chemistry. 262 (12): 5852–5856. doi:10.1016/s0021-9258(18)45652-9. PMID 3571237.
  29. ^ Keller U (July 1984). "Acyl pentapeptide lactone synthesis in actinomycin-producing streptomycetes by feeding with structural analogs of 4-methyl-3-hydroxyanthranilic acid". The Journal of Biological Chemistry. 259 (13): 8226–8231. doi:10.1016/s0021-9258(17)39717-x. PMID 6203903.
  30. ^ Pfennig F, Schauwecker F, Keller U (April 1999). "Molecular characterization of the genes of actinomycin synthetase I and of a 4-methyl-3-hydroxyanthranilic acid carrier protein involved in the assembly of the acylpeptide chain of actinomycin in Streptomyces". The Journal of Biological Chemistry. 274 (18): 12508–12516. doi:10.1074/jbc.274.18.12508. PMID 10212227.

External links edit

  • "Dactinomycin". Drug Information Portal. U.S. National Library of Medicine.

January 01, 1970
dactinomycin, also, known, actinomycin, chemotherapy, medication, used, treat, number, types, cancer, this, includes, wilms, tumor, rhabdomyosarcoma, ewing, sarcoma, trophoblastic, neoplasm, testicular, cancer, certain, types, ovarian, cancer, given, injection. Dactinomycin also known as actinomycin D is a chemotherapy medication used to treat a number of types of cancer 2 This includes Wilms tumor rhabdomyosarcoma Ewing s sarcoma trophoblastic neoplasm testicular cancer and certain types of ovarian cancer 2 It is given by injection into a vein 2 DactinomycinClinical dataTrade namesCosmegenOther namesActinomycin D2 Amino 4 6 dimethyl 3 oxo 3H phenoxazine 1 9 dicarboxylic acid bis 5 12 diisopropyl 9 13 16 trimethyl 4 7 11 14 17 pentaoxo hexadecahydro 10 oxa 3a 6 13 16 tetraaza cyclopentacyclohexadecen 8 yl amide AHFS Drugs comMonographMedlinePlusa682224PregnancycategoryAU DRoutes ofadministrationIVATC codeL01DA01 WHO Legal statusLegal statusAU S4 Prescription only CA only UK POM Prescription only US onlyPharmacokinetic dataProtein binding5 MetabolismhepaticElimination half life36 hoursExcretionBile 1 IdentifiersIUPAC name 2 Amino N N 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 4 7 10 13 oxatetraazacyclohexadecin 10 yl 4 6 dimethyl 3 oxo 3H phenoxazine 1 9 dicarboxamideCAS Number50 76 0 YPubChem CID2019DrugBankDB00970 NChemSpider10482167 YUNII1CC1JFE158KEGGC06770 NChEBICHEBI 27666 YChEMBLChEMBL1554 YNIAID ChemDB009885CompTox Dashboard EPA DTXSID9020031ECHA InfoCard100 000 058Chemical and physical dataFormulaC 62H 86N 12O 16Molar mass1255 438 g mol 13D model JSmol Interactive imageSMILES Cc1c2oc3c C ccc C O N C H 4C O N C H C C C C O N5CCC C H 5C O N C CC O N C C H C C C C O O C H 4C c3nc 2c C O N C H 2C O N C H C C C C O N3CCC C H 3C O N C CC O N C C H C C C C O O C H 2C c N c1 OInChI 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 YKey RJURFGZVJUQBHK IIXSONLDSA N Y N Y what is this verify Most people develop side effects 2 Common side effects include bone marrow suppression vomiting mouth ulcers hair loss liver problems infections and muscle pains 2 Other serious side effects include future cancers allergic reactions and tissue death if extravasation occurs 2 Use in pregnancy may harm the baby 2 Dactinomycin is in the cytotoxic antibiotic family of medications 3 It is believed to work by blocking the creation of RNA 2 Dactinomycin was approved for medical use in the United States in 1964 2 It is on the 2023 World Health Organization s List of Essential Medicines 4 Contents 1 Medical use 2 Side effects 3 Mechanism 4 History 5 Research use 6 Biosynthesis 7 References 8 External linksMedical use editActinomycin is a clear yellowish liquid administered intravenously and most commonly used in treatment of a variety of cancers including Gestational trophoblastic neoplasia 5 Wilms tumor 6 Rhabdomyosarcoma 7 Ewing s sarcoma 8 Malignant hydatidiform mole 9 Sometimes it will be combined with other drugs in chemotherapy regimens like the VAC regimen with vincristine and cyclophosphamide for treating rhabdomyosarcoma and Ewing s sarcoma 10 It is also used as a radiosensitizer in adjunct to radiotherapies 11 since it can increase the radiosensitivity of tumor cells by inhibiting repair of sublethal radiation damage and delay the onset of the compensatory hyperplasia that occurs following irradiation 12 Side effects editCommon adverse drug reaction includes bone marrow suppression fatigue hair loss mouth ulcer loss of appetite and diarrhea Actinomycin is a vesicant if extravasation occurs Mechanism editIn cell biology actinomycin D is shown to have the ability to inhibit transcription Actinomycin D does this by binding DNA at the transcription initiation complex and preventing elongation of RNA chain by RNA polymerase 13 History editActinomycin D was the first antibiotic shown to have anti cancer activity 14 It was first isolated by Selman Waksman and his co worker H Boyd Woodruff in 1940 15 using fermentation products from Streptomyces 16 It was approved by the U S Food and Drug Administration FDA on December 10 1964 17 and launched by Merck Sharp and Dohme under the trade name Cosmegen Research use editBecause actinomycin can bind DNA duplexes it can also interfere with DNA replication although other chemicals such as hydroxyurea are better suited for use in the laboratory as inhibitors of DNA synthesis 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 18 Biosynthesis editActinomycin D is composed of a central phenoxazinone chromophore tethered to two identical cyclic peptides and was first structurally characterized by Nuclear Magnetic Resonance NMR analysis in 1982 19 The biosynthesis of Actinomycin D has been under investigation since its discovery early fermentation feeding experiments revealed the roles of both tryptophan and D glutamate as precursor substrates 20 19 and strain mutagenesis experiments demonstrated that a phenoxazinone synthase enzyme might be responsible for coupling of two moieties of 4 methyl 3 hydroxyanthranilic acid 4 MHA into the final phenoxazinone structure 21 The 4 MHA substrate was shown to be produced from tryptophan through the action of enzymes such as tryptophan dioxygenase kynurenine formamidase kynurenine hydroxylase hydroxykynurenase and methyltransferase 22 23 Early experiments elucidated the presence of non ribosomal peptide synthetases 24 25 26 27 and subsequent purification and heterologous expression experiments 24 25 28 29 showed the acmD and acmA genes to be responsible for activation of the 4 MHA which then undergoes chain elongation through the action of the acmB and acmC genes In total the NRPS assembly line is composed of twenty two modules including two each of epimerase and methylase domains 30 23 Recent sequencing of the actinomycin D gene cluster in Streptomyces chrysomallus showed that the four NRPS genes were surrounded on both sides by the two clusters of the genes involved in the well studied kynurenine pathway and responsible for the production of 4 MHA from tryptophan with nine paralogs identified between the two clusters 23 nbsp Biosynthetic scheme of actinomycin D demonstrating the conversion of tryptophan to 4 MHA and the subsequent elongation by nonribosomal peptide synthetase assembly line genes Figure modified from Keller et al 2010 23 References edit Kwok KK Vincent EC Gibson JN 2017 Pharmacology and Therapeutics for Dentistry Mosby pp 530 562 doi 10 1016 B978 0 323 39307 2 00036 9 a b c d e f g h i Dactinomycin The American Society of Health System Pharmacists Archived from the original on 11 September 2017 Retrieved 8 December 2016 British national formulary BNF 69 69 ed British Medical Association 2015 p 582 ISBN 9780857111562 World Health Organization 2023 The selection and use of essential medicines 2023 web annex A World Health Organization model list of essential medicines 23rd list 2023 Geneva World Health Organization hdl 10665 371090 WHO MHP HPS EML 2023 02 Turan T Karacay O Tulunay G Boran N Koc S Bozok S Kose MF 2006 Results with EMA CO etoposide methotrexate actinomycin D cyclophosphamide vincristine chemotherapy in gestational trophoblastic neoplasia International Journal of Gynecological Cancer 16 3 1432 1438 doi 10 1111 j 1525 1438 2006 00606 x PMID 16803542 S2CID 32560653 D Angio GJ Evans A Breslow N Beckwith B Bishop H Farewell V et al May 1981 The treatment of Wilms tumor results of the Second National Wilms Tumor Study Cancer 47 9 2302 2311 doi 10 1002 1097 0142 19810501 47 9 lt 2302 aid cncr2820470933 gt 3 0 co 2 k PMID 6164480 Khatua S Nair CN Ghosh K November 2004 Immune mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma the unresolved issues Journal of Pediatric Hematology Oncology 26 11 777 779 doi 10 1097 00043426 200411000 00020 PMID 15543019 Jaffe N Paed D Traggis D Salian S Cassady JR November 1976 Improved outlook for Ewing s sarcoma with combination chemotherapy vincristine actinomycin D and cyclophosphamide and radiation therapy Cancer 38 5 1925 1930 doi 10 1002 1097 0142 197611 38 5 lt 1925 AID CNCR2820380510 gt 3 0 CO 2 J PMID 991106 Uberti EM Fajardo M Ferreira SV Pereira MV Seger RC Moreira MA et al December 2009 Reproductive outcome after discharge of patients with high risk hydatidiform mole with or without use of one bolus dose of actinomycin D as prophylactic chemotherapy during the uterine evacuation of molar pregnancy Gynecologic Oncology 115 3 476 481 doi 10 1016 j ygyno 2009 09 012 PMID 19818481 Arndt CA Stoner JA Hawkins DS Rodeberg DA Hayes Jordan AA Paidas CN et al 2009 Vincristine Actinomycin and Cyclophosphamide Compared With Vincristine Actinomycin and Cyclophosphamide Alternating With Vincristine Topotecan and Cyclophosphamide for Intermediate Risk Rhabdomyosarcoma Children s Oncology Group Study D9803 J Clin Oncol 27 31 5182 5188 doi 10 1200 JCO 2009 22 3768 PMC 2773476 PMID 19770373 Matthews NH Moustafa F Kaskas NM Robinson Bostom L Pappas Taffer L 2020 41 Dermatologic Toxicities of Anticancer Therapy Abeloff s Clinical Oncology Elsevier pp 621 648 doi 10 1016 B978 0 323 47674 4 00041 4 ISBN 9780323476744 S2CID 198317393 Hagemann RF Concannon JP April 1973 Mechanism of intestinal radiosensitization by actinomycin D The British Journal of Radiology 46 544 302 308 doi 10 1259 0007 1285 46 544 302 PMID 4720744 Sobell HM August 1985 Actinomycin and DNA transcription Proceedings of the National Academy of Sciences of the United States of America 82 16 5328 5331 Bibcode 1985PNAS 82 5328S doi 10 1073 pnas 82 16 5328 PMC 390561 PMID 2410919 Hollstein U 1974 Actinomycin Chemistry and mechanism of action Chemical Reviews 74 6 625 652 doi 10 1021 cr60292a002 Waksman SA Woodruff HB 1940 Bacteriostatic and bacteriocidal substances produced by soil actinomycetes Proceedings of the Society for Experimental Biology and Medicine 45 609 614 doi 10 3181 00379727 45 11768 S2CID 84774334 Dactinomycin LiverTox Clinical and Research Information on Drug Induced Liver Injury Internet National Institute of Diabetes and Digestive and Kidney Diseases 2012 PMID 31644085 Drugs FDA Dactinomycin FDA Retrieved 2023 10 15 Toba K Koike T Watanabe K Fuse I Takahashi M Hashimoto S et al January 2000 Cell kinetic study of normal human bone marrow hematopoiesis and acute leukemia using 7AAD PY European Journal of Haematology 64 1 10 21 doi 10 1034 j 1600 0609 2000 09005 x PMID 10680701 S2CID 41065740 a b Shafer RH Formica JV Delfini C Brown SC Mirau PA December 1982 Biosynthesis and characterization of 15N actinomycin D and conformational analysis by nitrogen 15 nuclear magnetic resonance Biochemistry 21 25 6496 6503 doi 10 1021 bi00268a027 PMID 6129895 Sivak A Katz E July 1962 Biosynthesis of the actinomycin chromophore Influence of alpha 4 5 and 6 methyl DL tryptophan on actinomycin synthesis Biochimica et Biophysica Acta 62 1 80 90 doi 10 1016 0006 3002 62 90493 6 PMID 13913519 Troost T Katz E March 1979 Phenoxazinone biosynthesis accumulation of a precursor 4 methyl 3 hydroxyanthranilic acid by mutants of Streptomyces parvulus Journal of General Microbiology 111 1 121 132 doi 10 1099 00221287 111 1 121 PMID 458423 Jones GH December 1987 Actinomycin synthesis in Streptomyces antibioticus enzymatic conversion of 3 hydroxyanthranilic acid to 4 methyl 3 hydroxyanthranilic acid Journal of Bacteriology 169 12 5575 5578 doi 10 1128 jb 169 12 5575 5578 1987 PMC 213988 PMID 2445729 a b c d Keller U Lang M Crnovcic I Pfennig F Schauwecker F May 2010 The actinomycin biosynthetic gene cluster of Streptomyces chrysomallus a genetic hall of mirrors for synthesis of a molecule with mirror symmetry Journal of Bacteriology 192 10 2583 2595 doi 10 1128 JB 01526 09 PMC 2863554 PMID 20304989 a b Schauwecker F Pfennig F Grammel N Keller U April 2000 Construction and in vitro analysis of a new bi modular polypeptide synthetase for synthesis of N methylated acyl peptides Chemistry amp Biology 7 4 287 297 doi 10 1016 s1074 5521 00 00103 4 PMID 10780924 a b Schauwecker F Pfennig F Schroder W Keller U May 1998 Molecular cloning of the actinomycin synthetase gene cluster from Streptomyces chrysomallus and functional heterologous expression of the gene encoding actinomycin synthetase II Journal of Bacteriology 180 9 2468 2474 doi 10 1128 jb 180 9 2468 2474 1998 PMC 107190 PMID 9573200 Stindl A Keller U May 1993 The initiation of peptide formation in the biosynthesis of actinomycin The Journal of Biological Chemistry 268 14 10612 10620 doi 10 1016 S0021 9258 18 82242 6 PMID 7683683 Stindl A Keller U August 1994 Epimerization of the D valine portion in the biosynthesis of actinomycin D Biochemistry 33 31 9358 9364 doi 10 1021 bi00197a041 PMID 8049237 Keller U April 1987 Actinomycin synthetases Multifunctional enzymes responsible for the synthesis of the peptide chains of actinomycin The Journal of Biological Chemistry 262 12 5852 5856 doi 10 1016 s0021 9258 18 45652 9 PMID 3571237 Keller U July 1984 Acyl pentapeptide lactone synthesis in actinomycin producing streptomycetes by feeding with structural analogs of 4 methyl 3 hydroxyanthranilic acid The Journal of Biological Chemistry 259 13 8226 8231 doi 10 1016 s0021 9258 17 39717 x PMID 6203903 Pfennig F Schauwecker F Keller U April 1999 Molecular characterization of the genes of actinomycin synthetase I and of a 4 methyl 3 hydroxyanthranilic acid carrier protein involved in the assembly of the acylpeptide chain of actinomycin in Streptomyces The Journal of Biological Chemistry 274 18 12508 12516 doi 10 1074 jbc 274 18 12508 PMID 10212227 External links edit Dactinomycin Drug Information Portal U S National Library of Medicine Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Dactinomycin amp oldid 1193311001, wikipedia, wiki, book, books, library,

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