放線菌素

放線菌素D
臨床資料
商品名（英語：Drug nomenclature）	Cosmegen
其他名稱	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.com	Monograph
MedlinePlus	a682224
懷孕分級	D;
給藥途徑	靜脈注射
ATC碼	L01DA01 (WHO) ;
法律規範狀態
法律規範	處方藥（℞-only）;
藥物動力學數據
血漿蛋白結合率	5%
生物半衰期	36小時
識別資訊
	IUPAC命名法 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號	50-76-0
PubChem CID	2019;
DrugBank	DB00970 ;
ChemSpider	10482167 ;
UNII	1CC1JFE158;
KEGG	C06770 ;
ChEBI	CHEBI:27666 ;
ChEMBL	ChEMBL1554 ;
NIAID ChemDB	009885;
CompTox Dashboard（英語：CompTox Chemicals Dashboard） (EPA)	DTXSID9020031 ;
ECHA InfoCard	100.000.058
化學資訊
化學式	C62H86N12O16
摩爾質量	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 ;

放線菌素D（英語：Actinomycin D或Dactinomycin，簡稱放線菌素，又名更生黴素）是從土壤中鏈黴菌屬的細菌分離出來的放線菌素類多肽類抗生素中最重要的一種。^[1] 作為早期的化療藥物之一，放線菌素已被使用了很長時間。

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歷史

放線菌素是人類發現的第一種具有抗癌作用的抗生素。^[1] 它最早是由賽爾曼·A·瓦克斯曼和他的同事H.B.伍德拉夫於1940年共同發現。^[2] 在1964年12月10日由美國FDA批准之後，放線菌素由默克藥廠以Cosmegen作為商品名銷售。

作用機理

在細胞生物學的研究中，人們發現放線菌素可以抑制轉錄過程。它能夠在轉錄起始複合物的位置結合DNA，與DNA形成複合體，阻止RNA聚合酶合成RNA。^[3]

臨床用途

臨床上用的放線菌素是清澈、黃色的液體，給藥方式為靜脈注射。它主要用來治療多種癌症，其中包括：

有時候放線菌素與其它化療藥物一同用於聯合化療，如用於治療橫紋肌肉瘤和尤因肉瘤的VAC聯合療法（與長春新鹼和環磷酰胺組成）。

放線菌素還被用作放射增敏劑，因為它能通過抑制癌細胞對亞致死輻射傷害的修復及延緩其在輻射之後的代償性增生，從而提高腫瘤對放療的敏感性。^[9]

副作用

常見的不良反應包括骨髓抑制、疲倦、脫髮、口腔潰瘍、食欲不振和腹瀉。^[10]

研究用途

由於可以和DNA雙螺旋結合，放線菌素除了抑制RNA合成之外，也能夠影響DNA複製。不過科學家一般會選擇更適合實驗室里使用的其它DNA複製抑制劑，如羥基脲。

放線菌素和它的熒光衍生物7-氨基放線菌素D（7-AAD）在流式細胞術研究和顯微鏡觀察細胞的過程中被用作染色劑。對富含GC的DNA片段的親和力使得它們特別適合於標記DNA。7-AAD還能與DNA單鏈結合，因此它還能用於觀察細胞凋亡和分辨活細胞與死細胞。^[11]

參考資料

[1]
Hollstein, U. Actinomycin. Chemistry and mechanism of action. Chemical Reviews. 1974, 74 (6): 625–652. doi:10.1021/cr60292a002.
[2]
Waksman S A, Woodruff H B. Bacteriostatic and bacteriocidal substances produced by soil actinomycetes. Proc Soc Exper Biol. 1940, 45: 609–614.
[3]
Sobell H. Actinomycin and DNA transcription. Proc Natl Acad Sci USA. 1985, 82 (16): 5328–31. PMC 390561 . PMID 2410919. doi:10.1073/pnas.82.16.5328.
[4]
Turan T, Karacay O, Tulunay G, Boran N, Koc S, Bozok S, Kose M. Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia. Int J Gynecol Cancer. 2006, 16 (3): 1432–8. PMID 16803542. doi:10.1111/j.1525-1438.2006.00606.x.
[5]
Abd El-Aal H, Habib E, Mishrif M. Wilms' Tumor: The Experience of the Pediatric Unit of Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine (NEMROCK). J Egypt Natl Canc Inst. 2005, 17 (4): 308–11. PMID 17102824.
[6]
Khatua S, Nair C, Ghosh K. Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues. J Pediatr Hematol Oncol. 2004, 26 (11): 777–9. PMID 15543019. doi:10.1097/00043426-200411000-00020.
[7]
Jaffe, N.; Paed, D.; Traggis, D.; Salian, S.; Cassady, J. R. Improved outlook for Ewing's sarcoma with combination chemotherapy (vincristine, actinomycin D and cyclophosphamide) and radiation therapy. Cancer. 1976, 38 (5): 1925–1930. PMID 991106. doi:10.1002/1097-0142(197611)38:5<1925::AID-CNCR2820380510>3.0.CO;2-J.
[8]
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. 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. 2009, 115 (3): 476–481. PMID 19818481. doi:10.1016/j.ygyno.2009.09.012.
[9]
Hagemann, R. F.; Concannon, J. P. Mechanism of intestinal radiosensitization by actinomycin D. British Journal of Radiology. 1973, 46 (544): 302–308. PMID 4720744. doi:10.1259/0007-1285-46-544-302.
[10]
孫燕. 抗肿瘤药物手册. 北京: 北京大學醫學出版社. 2006. ISBN 978-7-811-16205-9.
[11]
Toba, K.; Koike, T.; Watanabe, K.; Fuse, I.; Takahashi, M.; Hashimoto, S.; Takahashi, H.; Abe, T.; Yano, T. Cell kinetic study of normal human bone marrow hematopoiesis and acute leukemia using 7AAD/PY. European journal of haematology. 2000, 64 (1): 10–21. PMID 10680701. doi:10.1034/j.1600-0609.2000.09005.x.

外部連結

MedlinePlus上的藥物信息 medmaster-a682224

[gen-1] [1]
Hollstein, U. Actinomycin. Chemistry and mechanism of action. Chemical Reviews. 1974, 74 (6): 625–652. doi:10.1021/cr60292a002.

[2] [2]
Waksman S A, Woodruff H B. Bacteriostatic and bacteriocidal substances produced by soil actinomycetes. Proc Soc Exper Biol. 1940, 45: 609–614.

[3] [3]
Sobell H. Actinomycin and DNA transcription. Proc Natl Acad Sci USA. 1985, 82 (16): 5328–31. PMC 390561 . PMID 2410919. doi:10.1073/pnas.82.16.5328.

[4] [4]
Turan T, Karacay O, Tulunay G, Boran N, Koc S, Bozok S, Kose M. Results with EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine) chemotherapy in gestational trophoblastic neoplasia. Int J Gynecol Cancer. 2006, 16 (3): 1432–8. PMID 16803542. doi:10.1111/j.1525-1438.2006.00606.x.

[5] [5]
Abd El-Aal H, Habib E, Mishrif M. Wilms' Tumor: The Experience of the Pediatric Unit of Kasr El-Aini Center of Radiation Oncology and Nuclear Medicine (NEMROCK). J Egypt Natl Canc Inst. 2005, 17 (4): 308–11. PMID 17102824.

[6] [6]
Khatua S, Nair C, Ghosh K. Immune-mediated thrombocytopenia following dactinomycin therapy in a child with alveolar rhabdomyosarcoma: the unresolved issues. J Pediatr Hematol Oncol. 2004, 26 (11): 777–9. PMID 15543019. doi:10.1097/00043426-200411000-00020.

[7] [7]
Jaffe, N.; Paed, D.; Traggis, D.; Salian, S.; Cassady, J. R. Improved outlook for Ewing's sarcoma with combination chemotherapy (vincristine, actinomycin D and cyclophosphamide) and radiation therapy. Cancer. 1976, 38 (5): 1925–1930. PMID 991106. doi:10.1002/1097-0142(197611)38:5<1925::AID-CNCR2820380510>3.0.CO;2-J.

[8] [8]
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. 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. 2009, 115 (3): 476–481. PMID 19818481. doi:10.1016/j.ygyno.2009.09.012.

[9] [9]
Hagemann, R. F.; Concannon, J. P. Mechanism of intestinal radiosensitization by actinomycin D. British Journal of Radiology. 1973, 46 (544): 302–308. PMID 4720744. doi:10.1259/0007-1285-46-544-302.

[pku-10] [10]
孫燕. 抗肿瘤药物手册. 北京: 北京大學醫學出版社. 2006. ISBN 978-7-811-16205-9.

[11] [11]
Toba, K.; Koike, T.; Watanabe, K.; Fuse, I.; Takahashi, M.; Hashimoto, S.; Takahashi, H.; Abe, T.; Yano, T. Cell kinetic study of normal human bone marrow hematopoiesis and acute leukemia using 7AAD/PY. European journal of haematology. 2000, 64 (1): 10–21. PMID 10680701. doi:10.1034/j.1600-0609.2000.09005.x.

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