NAV

Novobiocin

Identification

Generic Name
Novobiocin
DrugBank Accession Number
DB01051
Background

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 In 2009, the FDA determined novobiocin sodium was withdrawn from sale for reasons of safety or effectiveness.6,7

Type
Small Molecule
Groups
Approved, Investigational, Vet approved, Withdrawn
Structure
3D
Similar Structures
Weight
Average: 612.6243
Monoisotopic: 612.231910004
Chemical Formula
C31H36N2O11
Synonyms
  • Albamycin
  • N-{7-[(3-O-carbamoyl-6-deoxy-5-methyl-4-O-methyl-β-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

Pharmacology

Indication

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

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug events
Improve clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
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 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.

TargetActionsOrganism
ADNA gyrase subunit B
inhibitor
Staphylococcus aureus
UDNA topoisomerase 1
inhibitor
Staphylococcus 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

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
Integrate drug-drug
interactions in your software
AbemaciclibNovobiocin may decrease the excretion rate of Abemaciclib which could result in a higher serum level.
AcamprosateThe excretion of Acamprosate can be decreased when combined with Novobiocin.
AcenocoumarolThe risk or severity of bleeding can be increased when Novobiocin is combined with Acenocoumarol.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be increased when used in combination with Novobiocin.
AcyclovirThe excretion of Acyclovir can be decreased when combined with Novobiocin.
Adefovir dipivoxilThe excretion of Adefovir dipivoxil can be decreased when combined with Novobiocin.
AfatinibNovobiocin may decrease the excretion rate of Afatinib which could result in a higher serum level.
AllopurinolThe excretion of Allopurinol can be decreased when combined with Novobiocin.
AlpelisibThe serum concentration of Alpelisib can be increased when it is combined with Novobiocin.
AmbrisentanThe excretion of Ambrisentan can be decreased when combined with Novobiocin.
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
Not Available

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Novobiocin sodiumQ9S9NQ5YIY1476-53-5WWPRGAYLRGSOSU-RNROJPEYSA-M

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
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
1-benzopyran / 1-hydroxy-2-unsubstituted benzenoid / 4-hydroxycoumarin / Acetal / Alcohol / Aromatic heteropolycyclic compound / Benzamide / Benzenoid / Benzoic acid or derivatives / Benzopyran
show 35 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
monocarboxylic acid amide, monosaccharide derivative, hexoside, hydroxycoumarin (CHEBI:28368) / Aromatic compounds (C05080)
Affected organisms
  • Enteric bacteria and other eubacteria

Chemical Identifiers

UNII
17EC19951N
CAS number
303-81-1
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[C@@H]1[C@@H](OC(N)=O)[C@@H](O)[C@H](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

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. [Article]
  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. [Article]
  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. [Article]
  4. CORBIN EE, PRIGOT A: Novobiocin; absorption, diffusion, and excretion studies. Antibiot Annu. 1956-1957:392-5. [Article]
  5. DAVID NA, BURGNER PR: Clinical effectiveness and safety of novobiocin. Antibiotic Med Clin Ther (New York). 1956 Apr;2(4):219-29. [Article]
  6. Federal Register: Determination That ALBAMYCIN (Novobiocin Sodium) Capsule, 250 Milligrams, Was Withdrawn From Sale for Reasons of Safety or Effectiveness [Link]
  7. Code of Federal Regulations 216.24: Drug products withdrawn or removed from the market for reasons of safety or effectiveness. [Link]
Human Metabolome Database
HMDB0015185
KEGG Compound
C05080
PubChem Compound
54675769
PubChem Substance
46507250
ChemSpider
10226117
BindingDB
50226181
RxNav
7538
ChEBI
28368
ChEMBL
CHEMBL36506
ZINC
ZINC000014879999
Therapeutic Targets Database
DAP001002
PharmGKB
PA164768819
PDBe Ligand
NOV
Wikipedia
Novobiocin
PDB Entries
1aj6 / 1kij / 1s14 / 3lps / 4urn / 4uro / 6b89 / 6mit / 6tbe / 6y8l …
show 3 more
MSDS
Download (73 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Not Yet RecruitingTreatmentMetastatic Malignant Solid Neoplasms / Unresectable Malignant Solid Neoplasm1
0TerminatedTreatmentOsteomyelitis1

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)5.51Chemaxon
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
Polarizability64.3 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

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details1. DNA gyrase subunit B
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. [Article]
  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. [Article]
Details2. DNA topoisomerase 1
Kind
Protein
Organism
Staphylococcus aureus
Pharmacological action
Unknown
Actions
Inhibitor
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. [Article]

Transporters

Details1. Solute carrier family 22 member 6
Kind
Protein
Organism
Humans
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. [Article]
Details2. Solute carrier family 22 member 8
Kind
Protein
Organism
Humans
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. [Article]
Details3. Solute carrier family 22 member 11
Kind
Protein
Organism
Humans
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. [Article]
Details4. ATP-binding cassette sub-family G member 2
Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]
  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. [Article]
Details5. Solute carrier organic anion transporter family member 1B1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]
Details6. Solute carrier organic anion transporter family member 1B3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]
Details7. Solute carrier organic anion transporter family member 2B1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as taurocholate, the prostaglandins PGD2, PGE1, PGE2, leukotriene C4, thromboxane B2 and iloprost.
Gene Name
SLCO2B1
Uniprot ID
O94956
Uniprot Name
Solute carrier organic anion transporter family member 2B1
Molecular Weight
76709.98 Da
References
  1. Karlgren M, Vildhede A, Norinder U, Wisniewski JR, Kimoto E, Lai Y, Haglund U, Artursson P: Classification of inhibitors of hepatic organic anion transporting polypeptides (OATPs): influence of protein expression on drug-drug interactions. J Med Chem. 2012 May 24;55(10):4740-63. doi: 10.1021/jm300212s. Epub 2012 May 15. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 03, 2023 17:47