Plicamycin

Plicamycin
Clinical data

AHFS/Drugs.com	Micromedex Detailed Consumer Information
Pregnancy category	US: X (Contraindicated)
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
Synonyms	Aureolic acid; Mithracin; Antibiotic LA 7017; Mithramycin A; Mitramycin; Plicatomycin
CAS Number	18378-89-7^Y
PubChem (CID)	5284610
DrugBank	DB06810^Y
ChemSpider	4447655^Y
UNII	NIJ123W41V^Y
KEGG	D00468^N
ChEMBL	CHEMBL509846^N
ECHA InfoCard	100.162.065
Chemical and physical data
Formula	C₅₂H₇₆O₂₄
Molar mass	1085.15 g/mol
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^Y Key:CFCUWKMKBJTWLW-GWRQQDNDSA-N^Y
^NY (what is this?) (verify)

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, 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. doi:10.1021/np980355k.
↑ 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. doi:10.1002/mpo.2950240511. PMID 7700186.
↑ Brown, John H.; Kennedy, B. J. (1965). "Mithramycin in the Treatment of Disseminated Testicular Neoplasms". New England Journal of Medicine. 272 (3): 111–8. doi:10.1056/NEJM196501212720301. PMID 14224214.
↑ 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. doi:10.1006/bbrc.1993.2178. PMID 8216256.
↑ 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. 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". Leuk. Res. 21 (5): 375–80. doi:10.1016/S0145-2126(96)00108-7. PMID 9225062.
↑ 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. doi:10.1158/1535-7163.MCT-06-0426. PMID 17121920.
↑ 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. doi:10.1097/CAD.0b013e3282a215e9. PMID 17893516.
↑ Majee, Sangita; Chakrabarti, Abhijit (1999). "Membrane interaction of an antitumor antibiotic, mithramycin, with anionic phospholipid vesicles". Biochemical Pharmacology. 57 (9): 981–7. doi:10.1016/S0006-2952(98)00374-8. PMID 10796068.

External links

Mithramycin A from Center for Pharmaceutical Research and Innovation

Intracellular chemotherapeutic agents / antineoplastic agents (L01)

SPs/MIs
(M phase)

Block microtubule assembly	Vinca alkaloids (Vinblastine^# Vincristine^# Vinflunine^§ Vindesine Vinorelbine)

Block microtubule disassembly	Taxanes (Cabazitaxel Docetaxel^# Larotaxel Ortataxel^† Paclitaxel^# Tesetaxel) Epothilones (Ixabepilone)

DNA replication
inhibitor

DNA precursors/
antimetabolites
(S phase)

Folic acid	Dihydrofolate reductase inhibitor (Aminopterin Methotrexate^# Pemetrexed Pralatrexate) Thymidylate synthase inhibitor (Raltitrexed Pemetrexed)

Purine	Adenosine deaminase inhibitor (Pentostatin) Halogenated/ribonucleotide reductase inhibitors (Cladribine Clofarabine Fludarabine) Nelarabine Thiopurine (Thioguanine^# Mercaptopurine^#)

Pyrimidine	Thymidylate synthase inhibitor (Fluorouracil^# Capecitabine Tegafur (+gimeracil/oteracil) Carmofur Floxuridine) DNA polymerase inhibitor (Cytarabine^#) Ribonucleotide reductase inhibitor (Gemcitabine) Hypomethylating agent (Azacitidine Decitabine)

Deoxyribonucleotide	Ribonucleotide reductase inhibitor (Hydroxycarbamide)

Topoisomerase inhibitors
(S phase)

I	Camptotheca (Camptothecin Cositecan^† Belotecan Gimatecan Exatecan Irinotecan Lurtotecan^‡ Silatecan^§ Topotecan Rubitecan^‡)

II	Podophyllum (Etoposide^# Teniposide)

II+Intercalation	Anthracyclines (Aclarubicin Daunorubicin^# Doxorubicin^# Epirubicin Idarubicin Amrubicin^† Pirarubicin Valrubicin Zorubicin) Anthracenediones (Mitoxantrone Pixantrone)

Crosslinking of DNA
(CCNS)

Alkylating	Nitrogen mustards: Mechlorethamine Cyclophosphamide^# (Ifosfamide Trofosfamide) Chlorambucil^# (Melphalan Prednimustine) Bendamustine Uramustine Estramustine Nitrosoureas: Carmustine Lomustine (Semustine) Fotemustine Nimustine Ranimustine Streptozocin Alkyl sulfonates: Busulfan (Mannosulfan Treosulfan) Aziridines: Carboquone ThioTEPA Triaziquone Triethylenemelamine

Platinum-based	Carboplatin Cisplatin Dicycloplatin Nedaplatin Oxaliplatin Satraplatin

Nonclassical	Hydrazines (Procarbazine^#) Triazenes (Dacarbazine^# Temozolomide) Altretamine Mitobronitol Pipobroman

Intercalation	Streptomyces (Actinomycin^# Bleomycin^# Mitomycin Plicamycin)

Photosensitizers/PDT

Other

Enzyme inhibitors	FI (Tipifarnib^§) CDK inhibitors (Alvocidib^† Seliciclib^† Palbociclib) PrI Bortezomib Carfilzomib Ixazomib PhI (Anagrelide) IMPDI (Tiazofurin^§) LI (Masoprocol) PARP inhibitor (Olaparib) HDAC (Belinostat Panobinostat Romidepsin Vorinostat) PIKI (Idelalisib)

Receptor antagonists	ERA (Atrasentan) Retinoid X receptor (Bexarotene) Sex steroid (Testolactone)

Other/ungrouped	Amsacrine Trabectedin Retinoids (Alitretinoin Tretinoin) Arsenic trioxide Asparagine depleters (Asparaginase^#/Pegaspargase) Celecoxib Demecolcine Elesclomol^§ Elsamitrucin Etoglucid Lonidamine Lucanthone Mitoguazone Mitotane Oblimersen^† Omacetaxine mepesuccinate Eribulin

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

This article is issued from Wikipedia - version of the 6/5/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.