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any of various red antibiotics isolated from soil bacteria

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/05 08:25:37」(JST)

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Dactinomycin. also known as actinomycin D, is the most significant member of actinomycines, which are a class of polypeptide antitumor antibiotics isolated from soil bacteria of the genus Streptomyces.^[1] It is one of the older anticancer drugs, and has been used for many years.

It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.^[2]

Medical use

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

Gestational trophoblastic neoplasia^[3]
Wilms' tumor^[4]
Rhabdomyosarcoma^[5]
Ewing's sarcoma^[6]
Malignant hydatidiform mole^[7]

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.

It is also used as a radiosensitizer in adjunct to radiotherapies, 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.^[8]

Side effects

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

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.^[9]

History

Actinomycin D was the first antibiotic shown to have anti-cancer activity.^[1] It was first isolated by Selman Waksman and his co-worker H. B. Woodruff in 1940.^[10] It was approved by the U.S. Food and Drug Administration (FDA) on December 10, 1964 and launched by Merck Sharp and Dohme under the trade name Cosmegen.

Research use

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.^[11]

References

^ ^a ^b Hollstein, U. (1974). "Actinomycin. Chemistry and mechanism of action". Chemical Reviews 74 (6): 625–652. doi:10.1021/cr60292a002.
^ "19th WHO Model List of Essential Medicines (April 2015)" (PDF). WHO. April 2015. Retrieved May 10, 2015.
^ Turan T, Karacay O, Tulunay G, Boran N, Koc S, Bozok S, Kose M (2006). "Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia". Int J Gynecol Cancer 16 (3): 1432–8. doi:10.1111/j.1525-1438.2006.00606.x. PMID 16803542.
^ D'Angio GJ, Evans A, Breslow N, Beckwith B, Bishop H, Farewell V, Goodwin W, Leape L, Palmer N, Sinks L, Sutow W, Tefft M, Wolff J (1981). "The treatment of Wilms' tumor: results of the Second National Wilms' Tumor Study.". Cancer 47 (9): 2302–11. doi:10.1002/1097-0142(19810501)47:9<2302::aid-cncr2820470933>3.0.co;2-k. PMID 6164480.
^ Khatua S, Nair C, Ghosh K (2004). "Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues". J Pediatr Hematol Oncol 26 (11): 777–9. doi:10.1097/00043426-200411000-00020. PMID 15543019.
^ Jaffe, N.; Paed, D.; Traggis, D.; Salian, S.; Cassady, J. R. (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.
^ Uberti, E. M. H.; Fajardo, M. D. C.; Ferreira, S. V. V. R.; Pereira, M. C. V.; Seger, R. C.; Moreira, M. A. L. R.; Torres, M. D.; De Nápoli, G.; Schmid, H. (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.
^ Hagemann, R. F.; Concannon, J. P. (1973). "Mechanism of intestinal radiosensitization by actinomycin D". British Journal of Radiology 46 (544): 302–308. doi:10.1259/0007-1285-46-544-302. PMID 4720744.
^ Sobell H (1985). "Actinomycin and DNA transcription". Proceedings of the National Academy of Sciences of the United States of America 82 (16): 5328–31. doi:10.1073/pnas.82.16.5328. PMC 390561. PMID 2410919.
^ Waksman S A, Woodruff H B (1940). "Bacteriostatic and bacteriocidal substances produced by soil actinomycetes". Proc Soc Exper Biol 45: 609–614.
^ Toba, K.; Koike, T.; Watanabe, K.; Fuse, I.; Takahashi, M.; Hashimoto, S.; Takahashi, H.; Abe, T.; Yano, T.; Shibazaki, Y.; Itoh, H.; Aizawa, Y. (2000). "Cell kinetic study of normal humanbone marrow hematopoiesis andacute leukemia using 7AAD/PY". European Journal of Haematology 64 (1): 10–21. doi:10.1034/j.1600-0609.2000.09005.x. PMID 10680701.

External links

MedlinePlus DrugInfo medmaster-a682224

UpToDate Contents

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1. 低リスク妊娠性絨毛腫瘍の初期マネージメント initial management of low risk gestational trophoblastic neoplasia
2. 抵抗性または再発性の妊娠性絨毛腫瘍のマネージメント management of resistant or recurrent gestational trophoblastic neoplasia
3. ユーイング肉腫ファミリーの腫瘍の治療 treatment of the ewing sarcoma family of tumors
4. 肝疾患を有する患者における化学療法による肝毒性および用量調整 chemotherapy hepatotoxicity and dose modification in patients with liver disease
5. 高リスク妊娠性絨毛腫瘍の初期マネージメント initial management of high risk gestational trophoblastic neoplasia

English Journal

Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells.

Hwang JS1, Kwon MY1, Kim KH1, Lee Y2, Lyoo IK2, Kim JE2, Oh ES3, Han IO4.
The Journal of biological chemistry.J Biol Chem.2017 Feb 3;292(5):1724-1736. doi: 10.1074/jbc.M116.737940. Epub 2016 Dec 7.
We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. At normal glucose concentrations, GlcN dose dependently increased LPS-stimulated production of NO/i
PMID 27927986

Cytotoxic conjugates of betulinic acid and substituted triazoles prepared by Huisgen Cycloaddition from 30-azidoderivatives.

Sidova V1, Zoufaly P1, Pokorny J1, Dzubak P2, Hajduch M2, Popa I1,2, Urban M1,2.
PloS one.PLoS One.2017 Feb 3;12(2):e0171621. doi: 10.1371/journal.pone.0171621. eCollection 2017.
In this work, we describe synthesis of conjugates of betulinic acid with substituted triazoles prepared via Huisgen 1,3-cycloaddition. All compounds contain free 28-COOH group. Allylic bromination of protected betulinic acid by NBS gave corresponding 30-bromoderivatives, their substitution with sodi
PMID 28158265

Etoposide, Methotrexate, and Dactinomycin Alternating With Cyclophosphamide and Vincristine (EMACO) for Male Patients With HCG-expressing, Chemoresistant Germ Cell Tumors.

Raggi D1, Giannatempo P, Miceli R, Farè E, Piva L, Biasoni D, Catanzaro M, Torelli T, Stagni S, Marongiu M, Gianni AM, Nicolai N, Salvioni R, Necchi A.
American journal of clinical oncology.Am J Clin Oncol.2017 Feb;40(1):60-65. doi: 10.1097/COC.0000000000000113.
OBJECTIVES: To retrospectively analyze the efficacy and safety results of the combination of methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMACO) regimen for patients with human chorionic gonadotropin (HCG)-producing germ cell tumors and who had failed multiple courses of chemothera
PMID 25089532

Japanese Journal

動注化学療法と子宮動脈塞栓術による保存的治療に成功した頸管妊娠の1例

八幡環,城道久,八木重孝 [他],南佐和子,井箟一彦
産婦人科の進歩 66(1), 18-23, 2014
… を認め当院受診し，経腟超音波検査で頸管内に胎児心拍を伴う胎嚢を認め，MRI所見と合わせて頸管妊娠と診断した．本症例は胎児心拍で，血中hCG値も15000mIU/mlと高値であり，妊孕性温存を希望していたためActinomycin-Dを用いた動注化学療法を選択し，また活動性出血をコントロールする目的で子宮動脈塞栓術を併用した．治療後，子宮頸管からの出血は減少し，第2病日には頸管内の胎嚢は消失した．治療に伴う重篤な有 …
NAID 130003391461

MEA療法が奏功した難治性非セミノーマ精巣腫瘍の1例

永井康晴,南高文,伊丹祥隆 [他],小林泰之,清水信貴,山本豊,林泰司,野澤昌弘,吉村一宏,石井徳味,植村天受
泌尿器科紀要 = Acta urologica Japonica 59(10), 693-697, 2013-10
… We experienced a case of testicular cancer that was successfully treated by salvage chemotherapy comprised of methotrexate, actinomycin D and etoposide (MEA). …
NAID 120005347148

Occurrence and biosynthesis of C-demethylactinomycins in actinomycin-producing Streptomyces chrysomallus and Streptomyces parvulus

CRNOVCIC Ivana,VATER Joachim,KELLER Ullrich
Journal of antibiotics 66(4), 211-218, 2013-04-25
NAID 10031168681

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★リンクテーブル★

リンク元	「アクチノマイシンD」「ACT」「Cosmegen」

「アクチノマイシンD」

Dactinomycin
Systematic (IUPAC) 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-dicarboxamide
Clinical data
Trade names	Cosmegen
AHFS/Drugs.com	monograph
MedlinePlus	a682224
Pregnancy; category	AU: D; US: D (Evidence of risk); ;
Legal status	AU: S4 (Prescription only); CA: ℞-only; UK: POM (Prescription only); US: ℞-only;
Routes of; administration	IV
Pharmacokinetic data
Protein binding	5%
Biological half-life	36 hours
Identifiers
CAS Number	50-76-0
ATC code	L01DA01
PubChem	CID: 2019
DrugBank	DB00970
ChemSpider	10482167
UNII	1CC1JFE158
KEGG	C06770
ChEBI	CHEBI:27666
ChEMBL	CHEMBL1554
NIAID ChemDB	009885
Synonyms	Actinomycin 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]
Chemical data
Formula	C62H86N12O16
Molecular mass	1255.42 g/mol
	InChI 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 ; Key:RJURFGZVJUQBHK-IIXSONLDSA-N ;
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