Plicamycin
Identification
- Generic Name
- Plicamycin
- DrugBank Accession Number
- DB06810
- Background
Plicamycin is an antineoplastic antibiotic produced by Streptomyces plicatus. It has been used in the treatment of testicular cancer, Paget's disease of bone, and, rarely, the management of hypercalcemia. The manufacturer discontinued plicamycin in 2000.
- Type
- Small Molecule
- Groups
- Approved, Investigational, Withdrawn
- Structure
- Weight
- Average: 1085.1454
Monoisotopic: 1084.47265336 - Chemical Formula
- C52H76O24
- Synonyms
- Aureolic acid
- Mithramycin
- Mithramycine
- Mithramycinum
- Plicamicina
- Plicamycin
- Plicamycine
- Plicamycinum
- External IDs
- A-2371
- ANTIBIOTIC LA-7017
- LA-7017
- NSC-24559
- PA-144
Pharmacology
- Indication
For the treatment of testicular cancer, as well as hypercalcemia and hypercalciuria associated with a variety of advanced forms of cancer.
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- Pharmacodynamics
Plicamycin is lethal to Hela cells in 48 hours at concentrations as low as 0.5 micrograms per milliliter of tissue culture medium. Plicamycin has shown significant anti-tumor activity against experimental leukemia in mice when administered intraperitoneally.
- Mechanism of action
Plicamycin is presumed to inhibit cellular and enzymic RNA synthesis by forming a complex with DNA. Plicamycin may also lower calcium serum levels by inhibiting the effect of parathyroid hormone upon osteoclasts or by blocking the hypercalcemic action of pharmacologic doses of vitamin D.
Target Actions Organism ADNA antagonistHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
There is no evidence of protein binding, nor is there any evidence of metabolism of the carbohydrate moiety of the drug to carbon dioxide and water with loss through respiration.
- Metabolism
- Not Available
- Route of elimination
Radioautography studies with 3H-labeled plicamycin in mice show that the greatest concentrations of the isotope are in the Kupffer cells of the liver and cells of the renal tubules. Plicamycin is rapidly cleared from the blood within the first 2 hours and excretion is also rapid. 67% percent of measured excretion occurs within 4 hours, 75% within 8 hours, and 90% is recovered in the first 24 hours after injection.
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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- Toxicity
The most important form of toxicity associated with the use of plicamycin consists of a dose-related bleeding syndrome which usually begins with an episode of epistaxis. Plicamycin crosses the blood-brain barrier; the concentration found in brain tissue is low but it persists longer than in other tissues.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Plicamycin is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Plicamycin is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Plicamycin is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Plicamycin is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Plicamycin is combined with Bupivacaine. - Food Interactions
- Not Available
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- International/Other Brands
- Mithracin (Pfizer)
Categories
- ATC Codes
- L01DC02 — Plicamycin
- Drug Categories
- Anthracyclines
- Antibiotics, Antineoplastic
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Calcium-Regulating Hormones and Agents
- Carbohydrates
- Coloring Agents
- Compounds used in a research, industrial, or household setting
- Cytotoxic Antibiotics and Related Substances
- Enzyme Inhibitors
- Fluorescent Dyes
- Glycosides
- Indicators and Reagents
- Laboratory Chemicals
- Luminescent Agents
- Naphthacenes
- Nucleic Acid Synthesis Inhibitors
- Protein Synthesis Inhibitors
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as oligosaccharides. These are carbohydrates made up of 3 to 10 monosaccharide units linked to each other through glycosidic bonds.
- Kingdom
- Organic compounds
- Super Class
- Organic oxygen compounds
- Class
- Organooxygen compounds
- Sub Class
- Carbohydrates and carbohydrate conjugates
- Direct Parent
- Oligosaccharides
- Alternative Parents
- Anthracenes / Naphthols and derivatives / O-glycosyl compounds / Tetralins / Aryl alkyl ketones / 1-hydroxy-4-unsubstituted benzenoids / Oxanes / Beta-hydroxy ketones / Acyloins / Vinylogous acids show 8 more
- Substituents
- 1-hydroxy-4-unsubstituted benzenoid / 1-naphthol / Acetal / Acyloin / Alcohol / Alpha-hydroxy ketone / Anthracene / Aromatic heteropolycyclic compound / Aryl alkyl ketone / Aryl ketone show 18 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- anthracycline antibiotic, carbohydrate-containing antibiotic, aureolic acid (CHEBI:31856)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- NIJ123W41V
- CAS number
- 18378-89-7
- InChI Key
- CFCUWKMKBJTWLW-BKHRDMLASA-N
- 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
- IUPAC Name
- (2S,3S)-3-[(1S,3S,4R)-3,4-dihydroxy-1-methoxy-2-oxopentyl]-2-{[(2S,4R,5R,6R)-4-{[(2S,4R,5S,6R)-4-{[(2S,4S,5R,6R)-4,5-dihydroxy-4,6-dimethyloxan-2-yl]oxy}-5-hydroxy-6-methyloxan-2-yl]oxy}-5-hydroxy-6-methyloxan-2-yl]oxy}-6-{[(2S,4R,5R,6R)-4-{[(2S,4R,5S,6R)-4,5-dihydroxy-6-methyloxan-2-yl]oxy}-5-hydroxy-6-methyloxan-2-yl]oxy}-8,9-dihydroxy-7-methyl-1,2,3,4-tetrahydroanthracen-1-one
- SMILES
- CO[C@@H]([C@@H]1CC2=CC3=CC(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)C(=O)[C@@H](O)[C@@H](C)O
References
- Synthesis Reference
Jurgen Rohr, Lily Remsing, Mohammad Nur-e-Alam, Jose Salas, Carmen Mendez, Alfredo Brana, Ana Gonzalez, "Derivatives of mithramycin and methods of making and uses thereof." U.S. Patent US20050192432, issued September 01, 2005.
US20050192432- General References
- Wohlert SE, Kunzel E, Machinek R, Mendez C, Salas JA, Rohr J: The structure of mithramycin reinvestigated. J Nat Prod. 1999 Jan;62(1):119-21. [Article]
- External Links
- Human Metabolome Database
- HMDB0015682
- KEGG Drug
- D00468
- KEGG Compound
- C12389
- PubChem Compound
- 163659
- PubChem Substance
- 99443298
- ChemSpider
- 143544
- 6995
- ChEBI
- 31856
- ChEMBL
- CHEMBL1237054
- PharmGKB
- PA165958411
- PDBe Ligand
- QWP
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Plicamycin
- PDB Entries
- 6vgg
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 2 Terminated Treatment Breast Cancer / Esophageal Cancer / Lung Cancer / Mesothelioma / Neoplasms, Gastrointestinal 1 1, 2 Terminated Treatment Esophageal Neoplasms / Lung Neoplasm / Mesothelioma / Neoplasm of thymus / Neoplasms, Embryonal Germ Cell Tumors 1 1, 2 Terminated Treatment Ewing's Sarcoma / Sarcomas 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 181.5 °C PhysProp - Predicted Properties
Property Value Source Water Solubility 1.3 mg/mL ALOGPS logP -0.23 ALOGPS logP 2.07 Chemaxon logS -2.9 ALOGPS pKa (Strongest Acidic) 7.84 Chemaxon pKa (Strongest Basic) -3.6 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 24 Chemaxon Hydrogen Donor Count 11 Chemaxon Polar Surface Area 358.2 Å2 Chemaxon Rotatable Bond Count 15 Chemaxon Refractivity 257.01 m3·mol-1 Chemaxon Polarizability 110.17 Å3 Chemaxon Number of Rings 8 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption - 0.6522 Blood Brain Barrier - 0.7202 Caco-2 permeable - 0.7222 P-glycoprotein substrate Substrate 0.8084 P-glycoprotein inhibitor I Non-inhibitor 0.7246 P-glycoprotein inhibitor II Non-inhibitor 0.7979 Renal organic cation transporter Non-inhibitor 0.9474 CYP450 2C9 substrate Non-substrate 0.829 CYP450 2D6 substrate Non-substrate 0.8772 CYP450 3A4 substrate Substrate 0.6129 CYP450 1A2 substrate Non-inhibitor 0.6673 CYP450 2C9 inhibitor Non-inhibitor 0.9692 CYP450 2D6 inhibitor Non-inhibitor 0.9228 CYP450 2C19 inhibitor Non-inhibitor 0.9555 CYP450 3A4 inhibitor Non-inhibitor 0.8839 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9814 Ames test Non AMES toxic 0.9133 Carcinogenicity Non-carcinogens 0.9528 Biodegradation Not ready biodegradable 0.9779 Rat acute toxicity 3.0601 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9888 hERG inhibition (predictor II) Non-inhibitor 0.8029
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 342.4118683 predictedDarkChem Lite v0.1.0 [M+H]+ 344.1045683 predictedDarkChem Lite v0.1.0 [M+Na]+ 340.8913683 predictedDarkChem Lite v0.1.0
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
References
- Fox KR, Howarth NR: Investigations into the sequence-selective binding of mithramycin and related ligands to DNA. Nucleic Acids Res. 1985 Dec 20;13(24):8695-714. [Article]
- Lombo F, Menendez N, Salas JA, Mendez C: The aureolic acid family of antitumor compounds: structure, mode of action, biosynthesis, and novel derivatives. Appl Microbiol Biotechnol. 2006 Nov;73(1):1-14. Epub 2006 Sep 30. [Article]
- Hampshire AJ, Fox KR: The effects of local DNA sequence on the interaction of ligands with their preferred binding sites. Biochimie. 2008 Jul;90(7):988-98. doi: 10.1016/j.biochi.2008.01.001. Epub 2008 Jan 11. [Article]
Drug created at September 14, 2010 16:21 / Updated at February 21, 2021 18:52