Mithramycin

Add time:08/31/2019    Source:sciencedirect.com

Mithramycin (also known as Plicamycin) is an antineoplastic antibiotic produced by Streptomyces plicatus. Mithramycin A is a DNA/RNA polymerase inhibitor, DNA-binding transcriptional inhibitor, antibiotic, and observed to facilitate tumor necrosis factor (TNF)-α and Fas ligand-induced apoptosis. As a DNA-binding transcriptional inhibitor, mithramycin A binds to GC-rich sequences located in the minor groove of DNA and is noted to be reversible and Mg2+-dependent. Additionally, mithramycin is used as a fluorescent dye in DNA-binding studies, as an antineoplastic agent, and to reduce hypercalcemia, especially due to malignancies. It is also often used to treat testicular cancer, Paget's disease of bone, and chronic myeloid leukemia. It is toxic to bone marrow, liver, and kidneys, and is used for treatment of advanced testicular carcinoma; major side effects are thrombocytopenia and hemorrhagic diathesis that can be life threatening. Upon exposure to this drug, it is concentrated in the Kupffer cells of the liver, in renal tubular cells, and along formed bone surfaces. A noted adverse effect has been its localization in areas of active bone resorption. Mithramycin also crosses the blood–brain barrier and enters the cerebrospinal fluid. It also has an inhibiting effect on osteoclasts and is used to treat hypercalcemia and hypercalciuria caused by metastatic malignancy. It is usually administered intravenously in clinical setting. LD50 doses for rat and mouse are 1.74 and 2.14 mg kg−1, respectively.

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