plicamycin
{{short description|Antibiotic}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 464208709
| 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
| image = Plicamycin.svg
| width = 300
| tradename =
| Drugs.com = {{drugs.com|CONS|plicamycin}}
| pregnancy_AU =
| pregnancy_US = X
| pregnancy_category =
| legal_AU =
| legal_CA =
| legal_UK =
| legal_US = Rx-only
| legal_status = discontinued
| routes_of_administration = Intravenous
| bioavailability =
| protein_bound =
| metabolism =
| elimination_half-life =
| excretion =
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 18378-89-7
| ATC_prefix = L01
| ATC_suffix = DC02
| PubChem = 5284610
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB06810
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4447655
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = NIJ123W41V
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D00468
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 509846
| C=52 | H=76 | O=24
| 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
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 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
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = CFCUWKMKBJTWLW-GWRQQDNDSA-N
| synonyms = Aureolic acid; Mithracin; Antibiotic LA 7017; Mithramycin A; Mitramycin; Plicatomycin
}}
Plicamycin (INN, also known as mithramycin; trade name Mithracin) is an antineoplastic antibiotic produced by Streptomyces plicatus. It is an RNA synthesis inhibitor.{{cite web |url=http://www.fermentek.com/Mithramycin_A|title=Mithramycin A |publisher=Fermentek}} 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.{{cite journal | vauthors = Wohlert SE, Künzel E, Machinek R, Méndez C, Salas JA, Rohr J | title = The structure of mithramycin reinvestigated | journal = Journal of Natural Products | volume = 62 | issue = 1 | pages = 119–121 | date = January 1999 | pmid = 9917296 | doi = 10.1021/np980355k }}
Uses
Plicamycin has been used in the treatment of testicular cancer,{{cite journal | vauthors = Kennedy BJ, Torkelson JL | title = Long-term follow-up of stage III testicular carcinoma treated with mithramycin (plicamycin) | journal = Medical and Pediatric Oncology | volume = 24 | issue = 5 | pages = 327–328 | date = May 1995 | pmid = 7700186 | doi = 10.1002/mpo.2950240511 }}{{cite journal | vauthors = Brown JH, Kennedy BJ | title = Mithramycin in the Treatment of Disseminated Testicular Neoplasms | journal = The New England Journal of Medicine | volume = 272 | issue = 3 | pages = 111–118 | date = January 1965 | pmid = 14224214 | doi = 10.1056/NEJM196501212720301 }} Paget's disease of bone,{{cite journal | vauthors = Hall TJ, Schaeublin M, Chambers TJ | title = The majority of osteoclasts require mRNA and protein synthesis for bone resorption in vitro | journal = Biochemical and Biophysical Research Communications | volume = 195 | issue = 3 | pages = 1245–1253 | date = September 1993 | pmid = 8216256 | doi = 10.1006/bbrc.1993.2178 }}{{cite journal | vauthors = Remsing LL, Bahadori HR, Carbone GM, McGuffie EM, Catapano CV, Rohr J | title = Inhibition of c-src transcription by mithramycin: structure-activity relationships of biosynthetically produced mithramycin analogues using the c-src promoter as target | journal = Biochemistry | volume = 42 | issue = 27 | pages = 8313–8324 | date = July 2003 | pmid = 12846580 | doi = 10.1021/bi034091z }} and, rarely, the management of hypercalcemia.
Plicamycin has been tested in chronic myeloid leukemia.{{cite journal | vauthors = Dutcher JP, Coletti D, Paietta E, Wiernik PH | title = A pilot study of alpha-interferon and plicamycin for accelerated phase of chronic myeloid leukemia | journal = Leukemia Research | volume = 21 | issue = 5 | pages = 375–380 | date = May 1997 | pmid = 9225062 | doi = 10.1016/S0145-2126(96)00108-7 }}
Plicamycin is currently used in multiple areas of research, including cancer cell apoptosis{{cite journal | vauthors = Lee TJ, Jung EM, Lee JT, Kim S, Park JW, Choi KS, Kwon TK | title = Mithramycin A sensitizes cancer cells to TRAIL-mediated apoptosis by down-regulation of XIAP gene promoter through Sp1 sites | journal = Molecular Cancer Therapeutics | volume = 5 | issue = 11 | pages = 2737–2746 | date = November 2006 | pmid = 17121920 | doi = 10.1158/1535-7163.MCT-06-0426 | doi-access = free }} and as a metastasis inhibitor.{{cite journal | vauthors = Lin RK, Hsu CH, Wang YC | title = Mithramycin A inhibits DNA methyltransferase and metastasis potential of lung cancer cells | journal = Anti-Cancer Drugs | volume = 18 | issue = 10 | pages = 1157–1164 | date = November 2007 | pmid = 17893516 | doi = 10.1097/CAD.0b013e3282a215e9 }}
One elucidated pathway shows it interacts by cross-binding chromatin GC-rich promoter motifs, thereby inhibiting gene transcription.{{cite journal | vauthors = Majee S, Chakrabarti A | title = Membrane interaction of an antitumor antibiotic, mithramycin, with anionic phospholipid vesicles | journal = Biochemical Pharmacology | volume = 57 | issue = 9 | pages = 981–987 | date = May 1999 | pmid = 10796068 | doi = 10.1016/S0006-2952(98)00374-8 }}
References
{{reflist}}
External links
- [https://web.archive.org/web/20151122093256/http://pharmacy.mc.uky.edu/cpri/snpa.php Mithramycin A from ] Center for Pharmaceutical Research and Innovation
{{Chemotherapeutic agents}}
{{Xenobiotic-sensing receptor modulators}}