{{short description|Antibiotic}} {{Drugbox | Verifiedfields = changed | verifiedrevid = 464208709 | IUPAC_name = (1''S'')-5-deoxy-1-''C''-((2''S'',3''S'')-7-{[2,6-dideoxy-3-''O''-(2,6-dideoxy-β-<small>D</small>-''arabino''-hexopyranosyl)-β-<small>D</small>-''arabino''-hexopyranosyl]oxy}-3-{[2,6-dideoxy-3-''C''-methyl-β-<small>D</small>-''ribo''-hexopyranosyl-(1→3)-2,6-dideoxy-β-<small>D</small>-''arabino''-hexopyranosyl-(1→3)-2,6-dideoxy-β-<small>D</small>-''arabino''-hexopyranosyl]oxy}-5,10-dihydroxy-6-methyl-4-oxo-1,2,3,4-tetrahydroanthracen-2-yl)-1-''O''-methyl-<small>D</small>-xylulose | image = Plicamycin.svg | image_class = skin-invert-image | width = 300
<!--Clinical data--> | tradename = | Drugs.com = {{drugs.com|CONS|plicamycin}} | pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> | pregnancy_US = X | pregnancy_category = | legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> | legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> | legal_UK = <!-- GSL / P / POM / CD / Class A, B, C --> | legal_US = Rx-only | legal_status = discontinued | routes_of_administration = Intravenous
<!--Pharmacokinetic data--> | bioavailability = | protein_bound = | metabolism = | elimination_half-life = | excretion =
<!--Identifiers--> | 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 | ChEBI = 31856 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = NIJ123W41V | KEGG_Ref = {{keggcite|changed|kegg}} | KEGG = D00468 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 509846
<!--Chemical data--> | 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.<ref>{{cite web |url=http://www.fermentek.com/Mithramycin_A|title=Mithramycin A |date=January 2004 |publisher=Fermentek}}</ref> 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.<ref>{{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 | bibcode = 1999JNAtP..62..119W | hdl = 10651/42580 | hdl-access = free }}</ref>
==Uses== Plicamycin has been used in the treatment of testicular cancer,<ref name="pmid7700186">{{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 }}</ref><ref>{{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 }}</ref> Paget's disease of bone,<ref>{{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 }}</ref><ref>{{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 }}</ref> and, rarely, the management of hypercalcemia.
Plicamycin has been tested in chronic myeloid leukemia.<ref name="pmid9225062">{{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 }}</ref>
Plicamycin is currently used in multiple areas of research, including cancer cell apoptosis<ref>{{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 }}</ref> and as a metastasis inhibitor.<ref>{{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 }}</ref>
One elucidated pathway shows it interacts by cross-binding chromatin GC-rich promoter motifs, thereby inhibiting gene transcription.<ref>{{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 }}</ref>
== 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}}
Category:DNA replication inhibitors