Identification

Name
Novobiocin
Accession Number
DB01051  (APRD00694)
Type
Small Molecule
Groups
Approved, Investigational, Vet Approved
Description

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) [PubChem]

Structure
Thumb
Synonyms
  • N-{7-[(3-O-carbamoyl-6-deoxy-5-methyl-4-O-methyl-beta-D-gulopyranosyl)oxy]-4-hydroxy-8-methyl-2-oxo-2H-chromen-3-yl}-4-hydroxy-3-(3-methylbut-2-en-1-yl)benzamide
  • Novobiocin
  • Novobiocina
  • Novobiocine
  • Novobiocinum
External IDs
Antibiotic PA-93
Product Ingredients
IngredientUNIICASInChI Key
Novobiocin sodiumQ9S9NQ5YIY1476-53-5WWPRGAYLRGSOSU-RNROJPEYSA-M
International/Other Brands
Albamycin
Categories
UNII
17EC19951N
CAS number
303-81-1
Weight
Average: 612.6243
Monoisotopic: 612.231910004
Chemical Formula
C31H36N2O11
InChI Key
YJQPYGGHQPGBLI-KGSXXDOSSA-N
InChI
InChI=1S/C31H36N2O11/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)/t23-,25+,26-,29-/m1/s1
IUPAC Name
(3R,4S,5R,6R)-5-hydroxy-6-({4-hydroxy-3-[4-hydroxy-3-(3-methylbut-2-en-1-yl)benzamido]-8-methyl-2-oxo-2H-chromen-7-yl}oxy)-3-methoxy-2,2-dimethyloxan-4-yl carbamate
SMILES
CO[[email protected]@H]1[[email protected]@H](OC(N)=O)[[email protected]@H](O)[[email protected]](OC2=C(C)C3=C(C=C2)C(O)=C(NC(=O)C2=CC=C(O)C(CC=C(C)C)=C2)C(=O)O3)OC1(C)C

Pharmacology

Indication

For the treatment of infections due to staphylococci and other susceptible organisms

Structured Indications
Not Available
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.

Mechanism of action

Novobiocin is an aminocoumarin. Aminocoumarins are very potent inhibitors of bacterial DNA gyrase and work by inhibiting the GyrB subunit of the enzyme involved in energy tranduction. Novobiocin as well as the other aminocoumarin antibiotics act as competitive inhibitors of the ATPase reaction catalysed by GyrB.

TargetActionsOrganism
ADNA gyrase subunit B
inhibitor
Staphylococcus aureus
UDNA topoisomerase 1Not AvailableStaphylococcus aureus
Absorption

Oral bioavailability is negligible.

Volume of distribution
Not Available
Protein binding

95%

Metabolism
Not Available
Route of elimination
Not Available
Half life

6 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Novobiocin.Investigational
Cholic AcidNovobiocin may decrease the excretion rate of Cholic Acid which could result in a higher serum level.Approved
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Novobiocin.Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Novobiocin.Approved
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Novobiocin.Approved, Investigational
Food Interactions
Not Available

References

Synthesis Reference

Jon Thorson, "Glycorandomization and Production of Novel Novobiocin Analogs." U.S. Patent US20120264924, issued October 18, 2012.

US20120264924
General References
  1. Vickers AA, Chopra I, O'Neill AJ: Intrinsic novobiocin resistance in Staphylococcus saprophyticus. Antimicrob Agents Chemother. 2007 Dec;51(12):4484-5. Epub 2007 Sep 17. [PubMed:17876001]
  2. Burlison JA, Neckers L, Smith AB, Maxwell A, Blagg BS: Novobiocin: redesigning a DNA gyrase inhibitor for selective inhibition of hsp90. J Am Chem Soc. 2006 Dec 6;128(48):15529-36. [PubMed:17132020]
  3. Singh G, Jayanarayan KG, Dey CS: Novobiocin induces apoptosis-like cell death in topoisomerase II over-expressing arsenite resistant Leishmania donovani. Mol Biochem Parasitol. 2005 May;141(1):57-69. [PubMed:15811527]
  4. CORBIN EE, PRIGOT A: Novobiocin; absorption, diffusion, and excretion studies. Antibiot Annu. 1956-1957:392-5. [PubMed:13425410]
  5. DAVID NA, BURGNER PR: Clinical effectiveness and safety of novobiocin. Antibiotic Med Clin Ther (New York). 1956 Apr;2(4):219-29. [PubMed:13303117]
External Links
Human Metabolome Database
HMDB15185
KEGG Compound
C05080
PubChem Compound
54675769
PubChem Substance
46507250
ChemSpider
10226117
BindingDB
50226181
ChEBI
28368
ChEMBL
CHEMBL36506
Therapeutic Targets Database
DAP001002
PharmGKB
PA164768819
HET
NOV
Wikipedia
Novobiocin
PDB Entries
1aj6 / 1kij / 1s14 / 3lps / 4urn / 4uro
MSDS
Download (73 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityInsolubleNot Available
logP4.1Not Available
pKa4.3MERCK INDEX (1996); pKa1
Predicted Properties
PropertyValueSource
Water Solubility0.00966 mg/mLALOGPS
logP3.07ALOGPS
logP3.26ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)6.96ChemAxon
pKa (Strongest Basic)-3.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area196.1 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity158.24 m3·mol-1ChemAxon
Polarizability63.97 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6404
Blood Brain Barrier-0.9659
Caco-2 permeable-0.654
P-glycoprotein substrateSubstrate0.7897
P-glycoprotein inhibitor INon-inhibitor0.5095
P-glycoprotein inhibitor IINon-inhibitor0.633
Renal organic cation transporterNon-inhibitor0.9687
CYP450 2C9 substrateNon-substrate0.8342
CYP450 2D6 substrateNon-substrate0.8536
CYP450 3A4 substrateSubstrate0.5931
CYP450 1A2 substrateNon-inhibitor0.8072
CYP450 2C9 inhibitorNon-inhibitor0.7263
CYP450 2D6 inhibitorNon-inhibitor0.872
CYP450 2C19 inhibitorNon-inhibitor0.7331
CYP450 3A4 inhibitorNon-inhibitor0.7934
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7844
Ames testNon AMES toxic0.5713
CarcinogenicityNon-carcinogens0.9321
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.2899 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9935
hERG inhibition (predictor II)Non-inhibitor0.9159
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-03di-0000009000-b1cde524a6fa9a8469fb
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-03di-0000449000-4b6598caa7dcff199d3c
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0230-0005904000-5fe18777e8a9abd4250a
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0a59-0096200000-4ea433cdc759c03b554d
LC-MS/MS Spectrum - LC-ESI-QTOF , negativeLC-MS/MSsplash10-0a4i-0091000000-912d33bd49e7c2686b5b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-03di-0141009000-46efbf9ab2bd123e3329
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000i-0900000000-e321cd21925818d2156a
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000i-0900000000-6425ec6e8bbb44075cf4
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000i-0900000000-32fb8ff4ec7fde30b513
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000i-0900000000-004f89ab3d920e8c5936
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-000j-0933000000-cd71bb412108d603ba2d

Taxonomy

Description
This compound belongs to the class of organic compounds known as coumarin glycosides. These are aromatic compounds containing a carbohydrate moiety glycosidically bound to a coumarin moiety.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Coumarins and derivatives
Sub Class
Coumarin glycosides
Direct Parent
Coumarin glycosides
Alternative Parents
Phenolic glycosides / 4-hydroxycoumarins / Hexoses / O-glycosyl compounds / 1-benzopyrans / Benzamides / Benzoyl derivatives / 1-hydroxy-2-unsubstituted benzenoids / Pyranones and derivatives / Oxanes
show 15 more
Substituents
Coumarin-7-o-glycoside / Coumarin o-glycoside / Phenolic glycoside / 4-hydroxycoumarin / Hydroxycoumarin / Hexose monosaccharide / O-glycosyl compound / Glycosyl compound / Benzopyran / 1-benzopyran
show 35 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
monocarboxylic acid amide, monosaccharide derivative, hexoside, hydroxycoumarin (CHEBI:28368) / Aromatic compounds (C05080)

Targets

Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
Yes
Actions
Inhibitor
General Function
Magnesium ion binding
Specific Function
DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, inc...
Gene Name
gyrB
Uniprot ID
P0A0K8
Uniprot Name
DNA gyrase subunit B
Molecular Weight
72539.365 Da
References
  1. Maxwell A: The interaction between coumarin drugs and DNA gyrase. Mol Microbiol. 1993 Aug;9(4):681-6. [PubMed:8231802]
  2. Gormley NA, Orphanides G, Meyer A, Cullis PM, Maxwell A: The interaction of coumarin antibiotics with fragments of DNA gyrase B protein. Biochemistry. 1996 Apr 16;35(15):5083-92. [PubMed:8664301]
Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
Unknown
General Function
Magnesium ion binding
Specific Function
Releases the supercoiling and torsional tension of DNA, which is introduced during the DNA replication and transcription, by transiently cleaving and rejoining one strand of the DNA duplex. Introdu...
Gene Name
topA
Uniprot ID
Q06AK7
Uniprot Name
DNA topoisomerase 1
Molecular Weight
79099.16 Da
References
  1. Tabary X, Moreau N, Dureuil C, Le Goffic F: Effect of DNA gyrase inhibitors pefloxacin, five other quinolones, novobiocin, and clorobiocin on Escherichia coli topoisomerase I. Antimicrob Agents Chemother. 1987 Dec;31(12):1925-8. [PubMed:2830840]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Saito H, Osumi M, Hirano H, Shin W, Nakamura R, Ishikawa T: Technical pitfalls and improvements for high-speed screening and QSAR analysis to predict inhibitors of the human bile salt export pump (ABCB11/BSEP). AAPS J. 2009 Sep;11(3):581-9. doi: 10.1208/s12248-009-9137-9. Epub 2009 Aug 18. [PubMed:19688600]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Duan P, You G: Novobiocin is a potent inhibitor for human organic anion transporters. Drug Metab Dispos. 2009 Jun;37(6):1203-10. doi: 10.1124/dmd.109.026880. Epub 2009 Mar 12. [PubMed:19282394]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Duan P, You G: Novobiocin is a potent inhibitor for human organic anion transporters. Drug Metab Dispos. 2009 Jun;37(6):1203-10. doi: 10.1124/dmd.109.026880. Epub 2009 Mar 12. [PubMed:19282394]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
Gene Name
SLC22A11
Uniprot ID
Q9NSA0
Uniprot Name
Solute carrier family 22 member 11
Molecular Weight
59970.945 Da
References
  1. Duan P, You G: Novobiocin is a potent inhibitor for human organic anion transporters. Drug Metab Dispos. 2009 Jun;37(6):1203-10. doi: 10.1124/dmd.109.026880. Epub 2009 Mar 12. [PubMed:19282394]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Gedeon C, Behravan J, Koren G, Piquette-Miller M: Transport of glyburide by placental ABC transporters: implications in fetal drug exposure. Placenta. 2006 Nov-Dec;27(11-12):1096-102. Epub 2006 Feb 3. [PubMed:16460798]
  2. Shiozawa K, Oka M, Soda H, Yoshikawa M, Ikegami Y, Tsurutani J, Nakatomi K, Nakamura Y, Doi S, Kitazaki T, Mizuta Y, Murase K, Yoshida H, Ross DD, Kohno S: Reversal of breast cancer resistance protein (BCRP/ABCG2)-mediated drug resistance by novobiocin, a coumermycin antibiotic. Int J Cancer. 2004 Jan 1;108(1):146-51. [PubMed:14618629]
  3. Elahian F, Kalalinia F, Behravan J: Evaluation of indomethacin and dexamethasone effects on BCRP-mediated drug resistance in MCF-7 parental and resistant cell lines. Drug Chem Toxicol. 2010 Apr;33(2):113-9. doi: 10.3109/01480540903390000. [PubMed:20307139]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:46