18378-89-7

Basic information

• Product Name: MITHRAMYCIN A
• Synonyms: AUREOLIC ACID;METHRAMYCIN A;MITHRACIN;MITHRAMYCIN;MITHRAMYCIN A;MITHRAMYCIN A, STREPTOMYCES PLICATUS;PLICAMYCIN;(2s-alpha,3beta(1r*,3r*4s*)))-droxy-7-methyl
• CAS NO: 18378-89-7
• Molecular Formula: C52H76O24
• Molecular Weight: 1085.15
• EINECS: 232-455-8
• Product Categories: Antibiotics;Antitumour;antibiotic
• Mol File: 18378-89-7.mol
• Article Data: 8

Chemical Properties

• Melting Point: 180-183 °C
• Boiling Point: 761.72°C (rough estimate)
• Flash Point: 327.4 °C
• Appearance: Red to brown/Powder
• Density: 1.1576 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.6500 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Soluble in DMSO (up to 20 mg/ml) or in Ethanol (up to 10 mg/ml)
• PKA: 4.54±0.60(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month.
• Merck: 13,7619
• BRN: 5236667
• CAS DataBase Reference: MITHRAMYCIN A(CAS DataBase Reference)
• NIST Chemistry Reference: MITHRAMYCIN A(18378-89-7)
• EPA Substance Registry System: MITHRAMYCIN A(18378-89-7)

Safety Data

• Hazard Codes: Xn,T+
• Statements: 22-26/27/28
• Safety Statements: 45-38-36/37/39-28A-22
• RIDADR: 3249
• WGK Germany: 3
• RTECS: PZ2800000
• F: 10
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 18378-89-7(Hazardous Substances Data)

Usage

Description

Mithramycin A, also known as Mithracin, is an antineoplastic antibiotic produced by Streptomyces plicatus. It belongs to the aureolic acid class of antitumor antibiotics and is known for its ability to inhibit both cancer growth and bone resorption by cross-linking GC-rich DNA, thus blocking the binding of Sp-family transcription factors to gene regulatory elements.
Used in Pharmaceutical Industry:
Mithramycin A is used as a transcription inhibitor for its ability to inhibit transcription and protein synthesis by non-covalent binding with G-C-rich duplex DNA in the presence of magnesium and zinc ions. This action makes it a potential candidate for targeting genes implicated in many human cancers and required for osteoclast-dependent bone resorption.
Mithramycin A is also used as an antitumor agent for its ability to induce differentiation of leukemic cells accompanied by an early decrease in c-myc expression, and selectively inhibit collagen-1 gene expression in human fibroblasts.
Additionally, Mithramycin A has been used to decrease bone resorption in patients with humoral hypercalcemia and Paget's disease, making it useful in the treatment of these conditions.
Chemical Properties:
Mithramycin A is a yellow powder with a chemical structure based on aureolic acid.
Brand Name:
Mithramycin A is marketed under the brand name Mithracin (Pfizer), with Mithramycin being a previously used name.

Indications

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.

Biological Activity

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.

Biochem/physiol Actions

Anticancer antibiotic. Inhibits transcription and protein synthesis. Binds to DNA in native chromatin. Substrate of Pgp in MDR phenotypes.

Purification Methods

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.]

Toxicity evaluation

Mithramycin inhibits mRNA and protein synthesis by adhering to DNA. Mithramycin appears to affect bone resorption by stimulating osteoclast activity and results in hypocalcemia and hypophosphatemia. It is believed to lower serum calcium concentrations, but the exact mechanism is unknown. It may act by blocking hypercalcemic action of vitamin D or by inhibiting the effect of parathyroid hormone on osteoclasts. Its inhibition of DNA-dependent RNA synthesis appears to render osteoclasts unable to fully respond to parathyroid hormone with the biosynthesis necessary for osteolysis.

References

1) Lin?et al. (2007),?Mithramycin A inhibits DNA methyltransferase and metastasis potential of lung cancer cells; Anticancer Drugs,?18?1157 2) Jia?et al.?(2010),?Combined treatment of pancreatic cancer cells with mithramycin A and tolfenamic acid promotes Sp1 degradation and synergistic anti-tumor activity; Cancer Res.,?70?1111 3) Lee?et al. (2006),?Mithramycin A sensitizes cancer cells to TRAIL-mediated apoptosis by down-regulation of XIAP gene promoter through Sp1 sites; Mol. Cancer Ther.,?5?2737

InChI:InChI=1/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

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