Plicamycin

Plicamycin
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
Pregnancy
category
  • US: X (Contraindicated)
Routes of
administration		 Intravenous
ATC code
Legal status
Legal status
Identifiers
Synonyms Aureolic acid; Mithracin; Antibiotic LA 7017; Mithramycin A; Mitramycin; Plicatomycin
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

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

  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.
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