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Novobiocin Sodium (formerly known as U6591, U-6591, Cathomycin, Inabiocin, Albadry, Streptonivicin, Albamycin) is a novel and potent antibiotic of the aminocoumarin class isolated from Streptomyces niveus and used for bacterial infections. It treats susceptible gram positive bacteria by acting on bacterial DNA gyrase (TopoIV). Additionally, novobiocin interacts with Hsp90, changing the chaperone's affinity for geldanamycin and radicicol and leading to the depletion of important regulatory Hsp90-dependent kinases such as v-Src, Raf-1, and p185 (ErbB2). Novobiocin prevents Hsp90 from being associated with the co-chaperones Hsc70 and p23.
Physicochemical Properties
| Molecular Formula | C31H35N2NAO11 | |
| Molecular Weight | 634.61 | |
| Exact Mass | 634.214 | |
| Elemental Analysis | C, 58.67; H, 5.56; N, 4.41; Na, 3.62; O, 27.73 | |
| CAS # | 1476-53-5 | |
| Related CAS # | 303-81-1 | |
| PubChem CID | 54675769 | |
| Appearance | White to off-white solid powder | |
| Density | 1.42g/cm3 | |
| Boiling Point | 848.2ºC at 760mmHg | |
| Melting Point | 215-220ºC | |
| Flash Point | 466.8ºC | |
| LogP | 4.838 | |
| Hydrogen Bond Donor Count | 5 | |
| Hydrogen Bond Acceptor Count | 11 | |
| Rotatable Bond Count | 9 | |
| Heavy Atom Count | 44 | |
| Complexity | 1150 | |
| Defined Atom Stereocenter Count | 4 | |
| SMILES | [Na+].O1C([H])([C@]([H])(C([H])([C@]([H])(C1(C([H])([H])[H])C([H])([H])[H])OC([H])([H])[H])OC(N([H])[H])=O)O[H])OC1C([H])=C([H])C2C(=C(C(=O)OC=2C=1C([H])([H])[H])N([H])C(C1C([H])=C([H])C(=C(C([H])([H])/C(/[H])=C(\C([H])([H])[H])/C([H])([H])[H])C=1[H])[O-])=O)O[H] |
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| InChi Key | WWPRGAYLRGSOSU-RNROJPEYSA-M | |
| InChi Code | InChI=1S/C31H36N2O11.Na/c1-14(2)7-8-16-13-17(9-11-19(16)34)27(37)33-21-22(35)18-10-12-20(15(3)24(18)42-28(21)38)41-29-23(36)25(43-30(32)39)26(40-6)31(4,5)44-29;/h7,9-13,23,25-26,29,34-36H,8H2,1-6H3,(H2,32,39)(H,33,37);/q;+1/p-1/t23-,25+,26-,29-;/m1./s1 | |
| Chemical Name | sodium;7-[(2R,3R,4S,5R)-4-carbamoyloxy-3-hydroxy-5-methoxy-6,6-dimethyloxan-2-yl]oxy-3-[[4-hydroxy-3-(3-methylbut-2-enyl)benzoyl]amino]-8-methyl-2-oxochromen-4-olate | |
| Synonyms |
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| HS Tariff Code | 2934.99.9001 | |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | β-lactam; HSP90 | |
| ln Vitro |
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| ln Vivo | In mice infected with Streptococcus pneumoniae that is resistant to amoxicillin, novobiocin sodium exhibits anti-infection activity. | |
| Cell Assay |
Cell lines: Cell-free assays Concentrations: 1 mM Incubation: Time 1 h Method: Reticulocyte lysate was treated with novobiocin for 1 h. |
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| Animal Protocol |
Female Swiss mice 100 or 200 mg/kg s.c. |
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| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Oral bioavailability is negligible. Patients with refractory cancer were treated with VP-16 on days 1, 3, and 5 /in a Phase 1 Clinical Trial/. Antiemetics, consisting of ondansetron and dexamethasone, were given 60 minutes before the VP-16 was administered. Novobiocin was given orally 30 minutes before the VP-16, and the dose was escalated in successive groups of patients according to a standard dose escalation design. Treatment cycles were repeated every 4 weeks. Plasma concentrations of novobiocin were determined during the first treatment cycle by high-performance liquid chromatography. Thirty-three patients were treated for a total of 69 cycles. Eleven patients were treated with a starting dose of VP-16 of 120 mg/sq m, and three of these patients experienced neutropenic fever. The dose of VP-16 was reduced to 100 mg/m2, and an additional 22 patients were enrolled. The dose of novobiocin ranged from 3 to 9 g. At a novobiocin dose of at least 5.5 g, plasma concentrations of at least 150 uM were sustained for 24 hours. Biological Half-Life 6 hours Novobiocin was given p.o. for 96 hr; 750 mg/sq m of i.v. cyclophosphamide was administered at 48 hr. Thirty-four patients received 65 courses. ... 18 of 19 patients treated at greater than or equal to 4 g daily had serum levels greater than or equal to 100 ug/ml at steady state, a level which corresponds to levels used in vitro and seen in vivo where the murine novobiocin half-life of 82 min is far less than that seen in humans (6.0 hr). |
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| Toxicity/Toxicokinetics |
Protein Binding 95% |
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| References |
[1]. J Biol Chem . 2000 Nov 24;275(47):37181-6. [2]. Biochemistry . 2004 Jun 29;43(25):8217-29. [3]. Mol Biochem Parasitol . 2005 May;141(1):57-69. [4]. IUBMB Life . 2010 Mar;62(3):194-9. [5]. Cell Physiol Biochem . 2014;33(3):670-80. [6]. Int J Antimicrob Agents . 2010 Jun;35(6):544-9. |
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| Additional Infomation |
Novobiocin is a coumarin-derived antibiotic obtained from Streptomyces niveus. It has a role as an antibacterial agent, an EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor, an antimicrobial agent, an Escherichia coli metabolite and a hepatoprotective agent. It is a hexoside, a monocarboxylic acid amide, a monosaccharide derivative, a hydroxycoumarin, an ether, a carbamate ester and a member of phenols. It is a conjugate acid of a novobiocin(1-). Novobiocin is an antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin. Novobiocin binds to DNA gyrase and blocks adenosine triphosphatase (ATPase) activity. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p189) Novobiocin sodium, a salt form of novobiocin, was initially approved in September 1964 and was indicated for the treatment of serious infections due to susceptible strains of Staphylococcus aureus when other less toxic antibiotics cannot be used. In 2009, the FDA determined novobiocin sodium was withdrawn from sale for reasons of safety or effectiveness. Novobiocin has been reported in Streptomyces, Streptomyces albidoflavus, and other organisms with data available. Novobiocin is an aminocoumarin antibiotic, produced by the actinomycete Streptomyces nivens, with antibacterial property. Novobiocin, as well as other aminocoumarin antibiotics, inhibits bacterial DNA synthesis by targeting at the bacteria DNA gyrase and the related enzyme DNA topoisomerase IV. This antibiotic was used to treat infections by gram-positive bacteria. An antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p189) See also: Novobiocin Sodium (has salt form); Novobiocin Calcium (has salt form). Drug Indication For the treatment of infections due to staphylococci and other susceptible organisms Mechanism of Action Novobiocin is an aminocoumarinthat works by inhibiting the GyrB subunit of the bacterial DNA gyrase enzyme involved in energy tranduction. Similar to other aminocoumarin antibiotics, it acts as a competitive inhibitor of the ATPase reaction catalysed by GyrB. Therapeutic Uses Mesh Heading: anti-bacterial agents, enzyme inhibitors MEDICATION (VET): Used to treat canine respiratory infections and prevent mastitis in dairy cattle. THERAP CAT: Antibacterial. THERAP CAT (VET): Antimicrobial Novobiocin is a narrow-spectrum antibiotic that may be bacteriostatic or bactericidal at higher concentrations. It is active mostly against gram-positive bacteria but also against a few gram-negative bacteria. ... Its main use is in combination with other agents for the treatment of bovine mastitis. Drug Warnings Consequential organ system manifestations associated with ...Novobiocin /include:/ Immune system- skin rash; GI system- nausea, vomiting, diarrhea; hematologic system- pancytopenia, hemolytic anemia. /from table/ Pharmacodynamics Novobiocin is an aminocoumarin antibiotic that was produced by the actinomycete Streptomyces niveus. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. Other antibiotics in the aminocoumarin class include coumermycin A1 and clorobiocin. |
Solubility Data
| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (157.58 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C). (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5758 mL | 7.8789 mL | 15.7577 mL | |
| 5 mM | 0.3152 mL | 1.5758 mL | 3.1515 mL | |
| 10 mM | 0.1576 mL | 0.7879 mL | 1.5758 mL |