Plicamycin

Plicamycin
Clinical data
Other names	Aureolic acid; Mithracin; Antibiotic LA 7017; Mithramycin A; Mitramycin; Plicatomycin
AHFS/Drugs.com	Micromedex Detailed Consumer Information
Routes of; administration	Intravenous
ATC code	L01DC02 (WHO) ;
Legal status
Legal status	US: ℞-only; discontinued;
Identifiers
	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;
CAS Number	18378-89-7 ;
PubChem CID	5284610;
DrugBank	DB06810 ;
ChemSpider	4447655 ;
UNII	NIJ123W41V;
KEGG	D00468 ;
ChEMBL	ChEMBL509846 ;
CompTox Dashboard (EPA)	DTXSID6023492 ;
ECHA InfoCard	100.162.065
Chemical and physical data
Formula	C52H76O24
Molar mass	1085.156 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CO[C@H](C(=O)[C@@H](O)[C@@H](C)O)C1Cc2cc3cc(O[C@H]4C[C@@H](O[C@H]5C[C@@H](O)[C@H](O)[C@@H](C)O5)[C@@H](O)[C@@H](C)O4)c(C)c(O)c3c(O)c2C(=O)[C@H]1O[C@H]1C[C@@H](O[C@H]2C[C@@H](O[C@H]3C[C@](C)(O)[C@H](O)[C@@H](C)O3)[C@H](O)[C@@H](C)O2)[C@H](O)[C@@H](C)O1;
	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 ;
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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 SE, Künzel E, Machinek R, Méndez C, Salas JA, Rohr J (January 1999). "The structure of mithramycin reinvestigated". Journal of Natural Products. 62 (1): 119–121. doi:10.1021/np980355k. PMID 9917296.
^ Kennedy BJ, Torkelson JL (May 1995). "Long-term follow-up of stage III testicular carcinoma treated with mithramycin (plicamycin)". Medical and Pediatric Oncology. 24 (5): 327–328. doi:10.1002/mpo.2950240511. PMID 7700186.
^ Brown JH, Kennedy BJ (January 1965). "Mithramycin in the Treatment of Disseminated Testicular Neoplasms". The New England Journal of Medicine. 272 (3): 111–118. doi:10.1056/NEJM196501212720301. PMID 14224214.
^ Hall TJ, Schaeublin M, Chambers TJ (September 1993). "The majority of osteoclasts require mRNA and protein synthesis for bone resorption in vitro". Biochemical and Biophysical Research Communications. 195 (3): 1245–1253. doi:10.1006/bbrc.1993.2178. PMID 8216256.
^ Remsing LL, Bahadori HR, Carbone GM, McGuffie EM, Catapano CV, Rohr J (July 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): 8313–8324. 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". Leukemia Research. 21 (5): 375–380. doi:10.1016/S0145-2126(96)00108-7. PMID 9225062.
^ Lee TJ, Jung EM, Lee JT, Kim S, Park JW, Choi KS, Kwon TK (November 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): 2737–2746. doi:10.1158/1535-7163.MCT-06-0426. PMID 17121920.
^ Lin RK, Hsu CH, Wang YC (November 2007). "Mithramycin A inhibits DNA methyltransferase and metastasis potential of lung cancer cells". Anti-Cancer Drugs. 18 (10): 1157–1164. doi:10.1097/CAD.0b013e3282a215e9. PMID 17893516.
^ Majee S, Chakrabarti A (May 1999). "Membrane interaction of an antitumor antibiotic, mithramycin, with anionic phospholipid vesicles". Biochemical Pharmacology. 57 (9): 981–987. doi:10.1016/S0006-2952(98)00374-8. PMID 10796068.

External links

Mithramycin A from Center for Pharmaceutical Research and Innovation

[1] "Mithramycin A". Fermentek.

[2] Wohlert SE, Künzel E, Machinek R, Méndez C, Salas JA, Rohr J (January 1999). "The structure of mithramycin reinvestigated". Journal of Natural Products. 62 (1): 119–121. doi:10.1021/np980355k. PMID 9917296.

[pmid7700186-3] Kennedy BJ, Torkelson JL (May 1995). "Long-term follow-up of stage III testicular carcinoma treated with mithramycin (plicamycin)". Medical and Pediatric Oncology. 24 (5): 327–328. doi:10.1002/mpo.2950240511. PMID 7700186.

[4] Brown JH, Kennedy BJ (January 1965). "Mithramycin in the Treatment of Disseminated Testicular Neoplasms". The New England Journal of Medicine. 272 (3): 111–118. doi:10.1056/NEJM196501212720301. PMID 14224214.

[5] Hall TJ, Schaeublin M, Chambers TJ (September 1993). "The majority of osteoclasts require mRNA and protein synthesis for bone resorption in vitro". Biochemical and Biophysical Research Communications. 195 (3): 1245–1253. doi:10.1006/bbrc.1993.2178. PMID 8216256.

[6] Remsing LL, Bahadori HR, Carbone GM, McGuffie EM, Catapano CV, Rohr J (July 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): 8313–8324. 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". Leukemia Research. 21 (5): 375–380. doi:10.1016/S0145-2126(96)00108-7. PMID 9225062.

[8] Lee TJ, Jung EM, Lee JT, Kim S, Park JW, Choi KS, Kwon TK (November 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): 2737–2746. doi:10.1158/1535-7163.MCT-06-0426. PMID 17121920.

[9] Lin RK, Hsu CH, Wang YC (November 2007). "Mithramycin A inhibits DNA methyltransferase and metastasis potential of lung cancer cells". Anti-Cancer Drugs. 18 (10): 1157–1164. doi:10.1097/CAD.0b013e3282a215e9. PMID 17893516.

[10] Majee S, Chakrabarti A (May 1999). "Membrane interaction of an antitumor antibiotic, mithramycin, with anionic phospholipid vesicles". Biochemical Pharmacology. 57 (9): 981–987. doi:10.1016/S0006-2952(98)00374-8. PMID 10796068.

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