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効能
抗悪性腫瘍薬
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説明
Mithramycin is an antineoplastic antibiotic produced by
Streptomyces plicatus. It is well known as the aureolic acid
antitumor antibiotic that inhibits both cancer growth and
bone resorption by cross-linking GC-rich DNA, thus
blocking binding of Sp-family transcription factors to
gene regulatory elements. Transcription of c-Src, a gene
implicated in many human cancers and required for
osteoclast-dependent bone resorption, is regulated by the
binding of Sp factors to specific elements in its promoter.
Therefore, this gene represents an important anticancer
target and a potential lead target through which mithramycin
displays action against osteoclastic bone resorption
via an unknown mechanism. Hazards of handling this
drug by the health-care personnel arise from a combination
of factors: (1) its inherent toxicity and (2) the extent
to which workers are exposed to the drug in the course of
carrying out their duties. This exposure may be through
inadvertent ingestion of the drug on foodstuffs (e.g.,
workers’ lunches), inhalation of drug dusts or droplets, or
direct skin contact. Mithramycin has been used to
decrease bone resorption in patients with humoral
hypercalcemia and Paget’s disease.
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化学的特性
yellow powder
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使用
Mithramycin was the first of the aureolic acid class of antitumour antibiotics, isolated from Streptomyces. Mithramycin inhibits transcription and protein synthesis by non-covalent binding with G-C-rich duplex DNA in the presence of magnesium and zinc ions. Mithramycin also induces differentiation of leukemic cells accompanied by an early decrease in c-myc expression, and selectively inhibits collagen-1 gene expression in human fibroblasts.
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主な応用
Mithramycin, recently renamed plicamycin, was found in the culture broth of Streptomyces argillaceus and S. tanashiensis by Abbott Laboratories in 1952. It is structurally related to chromomycin A3. Mithramycin shows strong inhibitory activity against malignant cells of human origin. It acts by inhibition of the DNA-directed RNA synthesis through binding with DNA. Mithramycin is used intravenously to treat cancers of the embryonal cells, seminoma, choriocarcinoma, etc.
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適応症
Plicamycin (mithramycin, Mithracin) is one of the chromomycin
group of antibiotics produced by Streptomyces
tanashiensis. Plicamycin binds to DNA and inhibits transcription.
It also inhibits resorption of bone by osteoblasts,
thus lowering serum calcium levels.Very little is
known about its distribution, metabolism, and excretion.
Because of its severe toxicity, plicamycin has limited clinical
utility.The major indication for plicamycin therapy is
in the treatment of life-threatening hypercalcemia associated
with malignancy. Plicamycin also can be used in
the palliative therapy of metastatic testicular carcinoma
when all other known active drugs have failed.
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一般的な説明
Chemical structure: aureolic acid
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生物活性
Anticancer antibiotic that selectively binds to G-C-rich DNA in the presence of Mg 2+ or Zn 2+ , inhibiting RNA and DNA polymerase action. Inhibits c-myc expression and induces myeloid differentiation of HL-60 promyelocytic leukemia cells.
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純化方法
Purify mithramycin A by crystallisation from CHCl3. It is soluble in MeOH, EtOH, Me2CO, EtOAc, Me2SO and H2O, and moderately soluble in CHCl3, but is slightly soluble in *C6H6 and Et2O. It is a fluorescent antitumour agent used in flow cytometry. [Thiem & Meyer Tetrahedron 37 551 1981, NMR: Yu et al. Nature 218 193 1968, Beilstein 17/1 V 672.]
