Plicamycin

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Plicamycin
Plicamycin.svg
Clinical data
Synonyms Aureolic acid; Mithracin; Antibiotic LA 7017; Mithramycin A; Mitramycin; Plicatomycin
AHFS/Drugs.com Micromedex Detailed Consumer Information
Pregnancy
category
  • US: X (Contraindicated)
Routes of
administration
Intravenous
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
ECHA InfoCard 100.162.065
Chemical and physical data
Formula C52H76O24
Molar mass 1085.15 g/mol
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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[edit]

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[edit]

  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. PMID 9917296. doi:10.1021/np980355k. 
  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. PMID 7700186. doi:10.1002/mpo.2950240511. 
  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. PMID 14224214. doi:10.1056/NEJM196501212720301. 
  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. PMID 8216256. doi:10.1006/bbrc.1993.2178. 
  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. PMID 12846580. doi:10.1021/bi034091z. 
  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. PMID 9225062. doi:10.1016/S0145-2126(96)00108-7. 
  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. PMID 17121920. doi:10.1158/1535-7163.MCT-06-0426. 
  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. PMID 17893516. doi:10.1097/CAD.0b013e3282a215e9. 
  10. ^ Majee, Sangita; Chakrabarti, Abhijit (1999). "Membrane interaction of an antitumor antibiotic, mithramycin, with anionic phospholipid vesicles". Biochemical Pharmacology. 57 (9): 981–7. PMID 10796068. doi:10.1016/S0006-2952(98)00374-8. 

External links[edit]