Identification
NameNovobiocin
Accession NumberDB01051  (APRD00694)
TypeSmall Molecule
GroupsApproved, 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 KeyDetails
Novobiocin sodiumQ9S9NQ5YIY 1476-53-5WWPRGAYLRGSOSU-RNROJPEYSA-MDetails
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AlbamycinNot Available
Brand mixturesNot Available
Categories
UNII17EC19951N
CAS number303-81-1
WeightAverage: 612.6243
Monoisotopic: 612.231910004
Chemical FormulaC31H36N2O11
InChI KeyYJQPYGGHQPGBLI-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[C@@H]1[C@@H](OC(N)=O)[C@@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.

TargetKindPharmacological actionActionsOrganismUniProt ID
DNA gyrase subunit BProteinyes
inhibitor
Staphylococcus aureusP0A0K8 details
DNA topoisomerase 1ProteinunknownNot AvailableStaphylococcus aureusQ06AK7 details
Related Articles
Absorption

Oral bioavailability is negligible.

Volume of distributionNot Available
Protein binding

95%

MetabolismNot Available
Route of eliminationNot Available
Half life

6 hours

ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of Bcg 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 InteractionsNot 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
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (73 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
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
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-03di-0000009000-b1cde524a6fa9a8469fbView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-03di-0000449000-4b6598caa7dcff199d3cView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0230-0005904000-5fe18777e8a9abd4250aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0a59-0096200000-4ea433cdc759c03b554dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0a4i-0091000000-912d33bd49e7c2686b5bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-03di-0141009000-46efbf9ab2bd123e3329View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0900000000-e321cd21925818d2156aView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0900000000-6425ec6e8bbb44075cf4View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0900000000-32fb8ff4ec7fde30b513View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000i-0900000000-004f89ab3d920e8c5936View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-000j-0933000000-cd71bb412108d603ba2dView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis 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.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassCoumarins and derivatives
Sub ClassCoumarin glycosides
Direct ParentCoumarin glycosides
Alternative ParentsPhenolic glycosides / 4-hydroxycoumarins / Hexoses / O-glycosyl compounds / 1-benzopyrans / Benzamides / Benzoyl derivatives / 1-hydroxy-2-unsubstituted benzenoids / Pyranones and derivatives / Oxanes
SubstituentsCoumarin-7-o-glycoside / Coumarin o-glycoside / Phenolic glycoside / 4-hydroxycoumarin / Hydroxycoumarin / Hexose monosaccharide / O-glycosyl compound / Glycosyl compound / Benzopyran / 1-benzopyran
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptorsmonocarboxylic 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, including catenanes and knotted rings.
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. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(...
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 molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
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, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
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 from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from t...
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 July 18, 2017 16:55