Identification
Name Plicamycin
Accession Number DB06810
Type small molecule
Description 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.
Structure
Categories (*)
Molecular Weight 1085.1454
Groups approved
Monoisotopic Weight 1084.47265336
Pharmacology
Indication For the treatment of testicular cancer, as well as hypercalcemia and hypercalciuria associated with a variety of advanced forms of cancer.
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.
Absorption 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.
Biotransformation 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.
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.
Affected organisms Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
DNA
Name DNA
Gene Name Not Available
Pharmacological action yes
Actions antagonist
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. - Pubmed
  • 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. - Pubmed
  • 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. Epub 2008 Jan 11. - Pubmed
DTHybrid score Not Available