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an antineoplastic drug (trade name Mithracin) used to treat cancer of the testes (同)Mithracin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/04/13 21:18:18」(JST)

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Plicamycin (INN, also known as mithramycin; trade name Mithracin) is an antineoplastic antibiotic produced by Streptomyces plicatus. It is an RNA synthesis inhibitor.^[1] The manufacturer discontinued production in 2000. Several different structures are currently reported in different places all with the same chromomycin core, but with different stereochemistry in the glycoside chain, a 1999 study has re-investigated the compound and proposed a revised structure. ^[2]

Uses

Plicamycin has been used in the treatment of testicular cancer,^[3]^[4] Paget's disease of bone,^[5]^[6] and, rarely, the management of hypercalcemia.

Plicamycin has been tested in chronic myeloid leukemia.^[7]

Plicamycin is currently used in multiple areas of research, including cancer cell apoptosis^[8] and as a metastasis inhibitor.^[9]

One elucidated pathway shows it interacts by cross-binding chromatin GC-rich promoter motifs, thereby inhibiting gene transcription.^[10]

References

^ "Mithramycin A". Fermentek.
^ Wohlert, S. E.; Künzel, E.; Machinek, R.; Méndez, C.; Salas, J. A.; Rohr, J. "The Structure of Mithramycin Reinvestigated". Journal of Natural Products 62 (1): 119–121. doi:10.1021/np980355k.
^ Kennedy BJ, Torkelson JL (May 1995). "Long-term follow-up of stage III testicular carcinoma treated with mithramycin (plicamycin)". Med. Pediatr. Oncol. 24 (5): 327–8. doi:10.1002/mpo.2950240511. PMID 7700186.
^ Brown, John H.; Kennedy, B. J. (1965). "Mithramycin in the Treatment of Disseminated Testicular Neoplasms". New England Journal of Medicine 272 (3): 111–8. doi:10.1056/NEJM196501212720301. PMID 14224214.
^ Hall, T; Schaeublin, M; Chambers, TJ (1993). "The Majority of Osteoclasts Require mRNA and Protein Synthesis for Bone Resorption in Vitro". Biochemical and Biophysical Research Communications 195 (3): 1245–53. doi:10.1006/bbrc.1993.2178. PMID 8216256.
^ Remsing, Lily L.; Bahadori, Hamid R.; Carbone, Giuseppina M.; McGuffie, Eileen M.; Catapano, Carlo V.; Rohr, Jürgen (2003). "Inhibition of c-src Transcription by Mithramycin: Structure−Activity Relationships of Biosynthetically Produced Mithramycin Analogues Using the c-src Promoter as Target". Biochemistry 42 (27): 8313–24. doi:10.1021/bi034091z. PMID 12846580.
^ Dutcher JP, Coletti D, Paietta E, Wiernik PH (May 1997). "A pilot study of alpha-interferon and plicamycin for accelerated phase of chronic myeloid leukemia". Leuk. Res. 21 (5): 375–80. doi:10.1016/S0145-2126(96)00108-7. PMID 9225062.
^ Lee, Tae-Jin; Jung, Eun Mi; Lee, Jung Tae; Kim, Shin; Park, Jong-Wook; Choi, Kyeong Sook; Kwon, Taeg Kyu (2006). "Mithramycin a sensitizes cancer cells to TRAIL-mediated apoptosis by down-regulation of XIAP gene promoter through Sp1 sites". Molecular Cancer Therapeutics 5 (11): 2737–46. doi:10.1158/1535-7163.MCT-06-0426. PMID 17121920.
^ Lin, Ruo-Kai; Hsu, Chun-Hua; Wang, Yi-Ching (2007). "Mithramycin a inhibits DNA methyltransferase and metastasis potential of lung cancer cells". Anti-Cancer Drugs 18 (10): 1157–64. doi:10.1097/CAD.0b013e3282a215e9. PMID 17893516.
^ Majee, Sangita; Chakrabarti, Abhijit (1999). "Membrane interaction of an antitumor antibiotic, mithramycin, with anionic phospholipid vesicles". Biochemical Pharmacology 57 (9): 981–7. doi:10.1016/S0006-2952(98)00374-8. PMID 10796068.

UpToDate Contents

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1. 骨パジェット病の治療 treatment of paget disease of bone
2. 成人の顔面紅潮に対するアプローチ approach to flushing in adults

English Journal

Aristolochic acid I and ochratoxin A differentially regulate VEGF expression in porcine kidney epithelial cells-The involvement of SP-1 and HIFs transcription factors.

Stachurska A, Kozakowska M, Jozkowicz A, Dulak J, Loboda A.SourceDepartment of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
Toxicology letters.Toxicol Lett.2011 Jul 28;204(2-3):118-26. Epub 2011 Apr 29.
Aristolochic acid I (AAI) and ochratoxin A (OTA) cause chronic kidney diseases. Recently, the contribution of hypoxic injuries and angiogenic disturbances to nephropathies has been suggested, but underlying mechanisms have not been fully clarified yet. In porcine kidney epithelial cell line, LLC-PK1
PMID 21554934

Nrf2-dependent induction of NQO1 in mouse aortic endothelial cells overexpressing catalase.

Lin X, Yang H, Zhou L, Guo Z.AbstractOverexpression of catalase has been shown to accelerate benzo(a)pyrene (BaP) detoxification in mouse aortic endothelial cells (MAECs). NAD(P)H:quinone oxidoreductase-1 (NQO1) is an enzyme that catalyzes BaP-quinone detoxification. Aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor-2 (Nrf2) are transcription factors that control NQO1 expression. Here, we investigated the effects of catalase overexpression on NQO1, Nrf2, and AhR expression. The levels of NQO1 mRNA and protein were comparable in MAECs isolated from wild-type and transgenic mice that overexpress human catalase (hCatTg). BaP treatment increased NQO1 mRNA and protein levels in both groups, with a significantly greater induction in hCatTg MAECs than in wild-type cells. BaP-induced NQO1 promoter activity was dramatically higher in hCatTg MAECs than in wild-type cells. Our data also showed that the basal level of AhR and the BaP-induced level of Nrf2 were significantly higher in hCatTg MAECs than in wild-type cells. Inhibition of specificity protein-1 (Sp1) binding to the AhR promoter region by mithramycin A reversed the enhancing effect of catalase overexpression on AhR expression. Knockdown of AhR by RNA interference diminished BaP-induced expression of Nrf2 and NQO1. Knockdown of Nrf2 significantly decreased NQO1 mRNA and protein levels in cells with or without BaP treatment. NQO1 promoter activity was abrogated by mutation of the Nrf2-binding site in this promoter. In contrast, mutation of the AhR-binding site in the NQO1 promoter did not affect the promoter activity. These results suggest that catalase overexpression upregulates BaP-induced NQO1 expression by enhancing the Sp1-AhR-Nrf2 signaling cascade.
Free radical biology & medicine.Free Radic Biol Med.2011 Jul 1;51(1):97-106. Epub 2011 Apr 17.
Overexpression of catalase has been shown to accelerate benzo(a)pyrene (BaP) detoxification in mouse aortic endothelial cells (MAECs). NAD(P)H:quinone oxidoreductase-1 (NQO1) is an enzyme that catalyzes BaP-quinone detoxification. Aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-relate
PMID 21569840

Japanese Journal

Low-dose mithramycin exerts its anticancer effect via the p53 signaling pathway and synergizes with nutlin-3 in gynecologic cancers

OHGAMI Tatsuhiro,KATO Kiyoko,KOBAYASHI Hiroaki,SONODA Kenzo,INOUE Takafumi,YAMAGUCHI Shin-ichiro,YONEDA Tomoko,WAKE Norio
Cancer science 101(6), 1387-1395, 2010-06-10
NAID 10026593277

P3-76 Sp1阻害剤(mithramycin)の婦人科癌細胞増殖抑制機構の解析(Group86 悪性腫瘍全般5,一般演題,第61回日本産科婦人科学会学術講演会)

大神達寛,加藤聖子,小林裕明,山口真一郎,米田智子,和氣徳夫
日本産科婦人科學會雜誌 61(2), 693, 2009-02-01
NAID 110007166504

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★リンクテーブル★

リンク元	「ミトラマイシン」「KAP STEP2CK2008 001」

「ミトラマイシン」

Plicamycin
Systematic (IUPAC) name
	(1S)-5-deoxy-1-C-((2S,3S)-7-{[2,6-dideoxy-3-O-(2,6-dideoxy-β-D-arabino-hexopyranosyl)-β-D-arabino-hexopyranosyl]oxy}-3-{[2,6-dideoxy-3-C-methyl-β-D-ribo-hexopyranosyl-(1→3)-2,6-dideoxy-β-D-arabino-hexopyranosyl-(1→3)-2,6-dideoxy-β-D-arabino-hexopyranosyl]oxy}-5,10-dihydroxy-6-methyl-4-oxo-1,2,3,4-tetrahydroanthracen-2-yl)-1-O-methyl-D-xylulose
Clinical data
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy; category	US: X (Contraindicated);
Legal status	US: ℞-only; discontinued;
Routes of; administration	Intravenous
Identifiers
CAS Registry Number	18378-89-7
ATC code	L01DC02
PubChem	CID 5284610
DrugBank	DB06810
ChemSpider	4447655
UNII	NIJ123W41V
KEGG	D00468
ChEMBL	CHEMBL509846
Synonyms	Aureolic acid; Mithracin; Antibiotic LA 7017; Mithramycin A; Mitramycin; Plicatomycin
Chemical data
Formula	C52H76O24
Molecular mass	1085.15 g/mol
	InChI InChI=1S/C52H76O24/c1-18-29(72-34-14-30(43(58)21(4)68-34)73-33-13-28(54)42(57)20(3)67-33)12-26-10-25-11-27(49(66-9)48(63)41(56)19(2)53)50(47(62)39(25)46(61)38(26)40(18)55)76-36-16-31(44(59)23(6)70-36)74-35-15-32(45(60)22(5)69-35)75-37-17-52(8,65)51(64)24(7)71-37/h10,12,19-24,27-28,30-37,41-45,49-51,53-61,64-65H,11,13-17H2,1-9H3/t19-,20-,21-,22-,23-,24-,27?,28-,30-,31-,32-,33+,34+,35+,36+,37+,41+,42-,43+,44-,45-,49+,50+,51-,52+/m1/s1 ; Key:CFCUWKMKBJTWLW-GWRQQDNDSA-N ;
(what is this?) (verify)

　　[★]

英: mithramycin
同: プリカマイシン plicamycin

抗悪性腫瘍薬

特徴

クロモマイシン系
日本では市販されていない (SPC.419)

構造

作用機序

薬理作用

骨吸収抑制

抗菌スペクトル

動態

適応

抗腫瘍薬

testicular tumor

高カルシウム血症　←　副作用のためパミドロネートに取って代わられた(ICU.560)

注意

禁忌

副作用

骨髄抑制

「KAP STEP2CK2008 001」

　　[★]

Internal medicine 1-10

glossary

dysplastic nevus syndrome
bleomycin 肺線維症
cisplatin tinnititus, hearing loos, nephrotoxicity
mithramycin
cavaderis
エンテロバクター属。グラム陰性桿菌だよ
モラクセラ・カタラーリスってどんなやつ？

悪性黒色腫を疑う場合はABCD

asymmetry
border irregular
color variegation
diameter > 0.6cm

[1] "Mithramycin A". Fermentek.

[2] Wohlert, S. E.; Künzel, E.; Machinek, R.; Méndez, C.; Salas, J. A.; Rohr, J. "The Structure of Mithramycin Reinvestigated". Journal of Natural Products 62 (1): 119–121. doi:10.1021/np980355k.

[pmid7700186-3] Kennedy BJ, Torkelson JL (May 1995). "Long-term follow-up of stage III testicular carcinoma treated with mithramycin (plicamycin)". Med. Pediatr. Oncol. 24 (5): 327–8. doi:10.1002/mpo.2950240511. PMID 7700186.

[4] Brown, John H.; Kennedy, B. J. (1965). "Mithramycin in the Treatment of Disseminated Testicular Neoplasms". New England Journal of Medicine 272 (3): 111–8. doi:10.1056/NEJM196501212720301. PMID 14224214.

[5] Hall, T; Schaeublin, M; Chambers, TJ (1993). "The Majority of Osteoclasts Require mRNA and Protein Synthesis for Bone Resorption in Vitro". Biochemical and Biophysical Research Communications 195 (3): 1245–53. doi:10.1006/bbrc.1993.2178. PMID 8216256.

[6] Remsing, Lily L.; Bahadori, Hamid R.; Carbone, Giuseppina M.; McGuffie, Eileen M.; Catapano, Carlo V.; Rohr, Jürgen (2003). "Inhibition of c-src Transcription by Mithramycin: Structure−Activity Relationships of Biosynthetically Produced Mithramycin Analogues Using the c-src Promoter as Target". Biochemistry 42 (27): 8313–24. doi:10.1021/bi034091z. PMID 12846580.

[pmid9225062-7] Dutcher JP, Coletti D, Paietta E, Wiernik PH (May 1997). "A pilot study of alpha-interferon and plicamycin for accelerated phase of chronic myeloid leukemia". Leuk. Res. 21 (5): 375–80. doi:10.1016/S0145-2126(96)00108-7. PMID 9225062.

[8] Lee, Tae-Jin; Jung, Eun Mi; Lee, Jung Tae; Kim, Shin; Park, Jong-Wook; Choi, Kyeong Sook; Kwon, Taeg Kyu (2006). "Mithramycin a sensitizes cancer cells to TRAIL-mediated apoptosis by down-regulation of XIAP gene promoter through Sp1 sites". Molecular Cancer Therapeutics 5 (11): 2737–46. doi:10.1158/1535-7163.MCT-06-0426. PMID 17121920.

[9] Lin, Ruo-Kai; Hsu, Chun-Hua; Wang, Yi-Ching (2007). "Mithramycin a inhibits DNA methyltransferase and metastasis potential of lung cancer cells". Anti-Cancer Drugs 18 (10): 1157–64. doi:10.1097/CAD.0b013e3282a215e9. PMID 17893516.

[10] Majee, Sangita; Chakrabarti, Abhijit (1999). "Membrane interaction of an antitumor antibiotic, mithramycin, with anionic phospholipid vesicles". Biochemical Pharmacology 57 (9): 981–7. doi:10.1016/S0006-2952(98)00374-8. PMID 10796068.

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案内

mithramycin