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targets (1) transporters (5)
for drugs
Identification
Name Novobiocin
Accession Number DB01051 (APRD00694)
Type small molecule
Groups 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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Antibiotic Pa-93
  • Crystallinic Acid
  • NOV
  • Novobiocina [INN-Spanish]
  • Novobiocine [INN-French]
  • Novobiocinum [INN-Latin]
Brand names
  • Albamix
  • Albamycin
  • Cardelmycin
  • Cathocin
  • Cathomycin
  • Inamycin
  • Novo-R
  • Robiocina
  • Sirbiocina
  • Spheromycin
  • Stilbiocina
  • Streptonivicin
Brand name mixtures
  • Albacillin Suspension (Novobiocin (Novobiocin Sodium) + Penicillin G Procaine)
  • Delta-Albaplex Tablets (Novobiocin (Novobiocin Sodium) + Prednisolone + Tetracycline Hydrochloride)
  • Novodry Plus Suspension (Novobiocin (Novobiocin Sodium) + Penicillin G Procaine)
  • Special Formula 17900-Forte Suspension (Dihydrostreptomycin (Dihydrostreptomycin Sulfate) + Hydrocortisone Acetate + Hydrocortisone Sodium Succinate + Novobiocin (Novobiocin Sodium) + Penicillin G Procaine + Polymyxin B Sulfate)
Categories
  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Nucleic Acid Synthesis Inhibitors
CAS number 303-81-1
Weight Average: 612.6243
Monoisotopic: 612.231910004
Chemical Formula C31H36N2O11
InChI Key InChIKey=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
Plain Text
IUPAC Name
(3R,4S,5R,6R)-5-hydroxy-6-[(4-hydroxy-3-{[4-hydroxy-3-(3-methylbut-2-en-1-yl)benzene]amido}-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(CC=C(C)C)=C(O)C=C2)C(=O)O3)OC1(C)C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Carbohydrates
  • Chromones
Substructures
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Pyrans
  • Acetals and Derivatives
  • Carbamates and Derivatives
  • Phenols and Derivatives
  • Amino Ketones
  • Carbohydrates
  • Ethers
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Chromones
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Benzoyl Derivatives
  • Alcohols and Polyols
  • Phenyl Esters
  • Benzamides
Pharmacology
Indication For the treatment of infections due to staphylococci and other susceptible organisms
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.
Absorption Oral bioavailability is negligible.
Volume of distribution Not Available
Protein binding 95%
Metabolism
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
Pharmacoeconomics
Manufacturers
  • Pharmacia and upjohn co
Packagers Not Available
Dosage forms
Form Route Strength
Injection, powder, for solution Intravenous
Prices Not Available
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility Insoluble PhysProp
logP 4.1 PhysProp
pKa 4.3 Various sources
Predicted Properties
Property Value Source
water solubility 9.66e-03 g/l ALOGPS
logP 3.07 ALOGPS
logP 3.26 ChemAxon Molconvert
logS -4.80 ALOGPS
pKa 8.27 ChemAxon Molconvert
hydrogen acceptor count 9 ChemAxon Molconvert
hydrogen donor count 5 ChemAxon Molconvert
polar surface area 196.10 ChemAxon Molconvert
rotatable bond count 9 ChemAxon Molconvert
refractivity 158.24 ChemAxon Molconvert
polarizability 63.97 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Vickers AA, Chopra I, O’neill AJ: Intrinsic novobiocin resistance in Staphylococcus saprophyticus. Antimicrob Agents Chemother. 2007 Sep 17;. Pubmed
  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
  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
  4. CORBIN EE, PRIGOT A: Novobiocin; absorption, diffusion, and excretion studies. Antibiot Annu. 1956-1957;:392-5. Pubmed
  5. DAVID NA, BURGNER PR: Clinical effectiveness and safety of novobiocin. Antibiotic Med Clin Ther. 1956 Apr;2(4):219-29. Pubmed
External Links
Resource Link
KEGG Compound C05080 Link_out
PubChem Compound 9346 Link_out
PubChem Substance 46507250 Link_out
ChemSpider 8981 Link_out
BindingDB 282 Link_out
Therapeutic Targets Database DAP001002 Link_out
HET NOV Link_out
Drug Product Database 0 Link_out
Wikipedia http://en.wikipedia.org/wiki/Novobiocin Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (73 KB)
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. DNA gyrase subunit B

Pharmacological action: yes
Actions: inhibitor

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

Organism class: bacterial
UniProt ID: P0A0K8 Link_out
Gene: gyrB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Maxwell A: The interaction between coumarin drugs and DNA gyrase. Mol Microbiol. 1993 Aug;9(4):681-6. Pubmed
  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
Transporters

1. Bile salt export pump

Actions: inhibitor

Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes

UniProt ID: O95342 Link_out
Gene: ABCB11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Aug 18. Pubmed

2. Solute carrier family 22 member 6

Actions: inhibitor
UniProt ID: Q4U2R8 Link_out
Gene: hROAT1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Mar 12. Pubmed

3. Solute carrier family 22 member 8

Actions: inhibitor

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)

UniProt ID: Q8TCC7 Link_out
Gene: SLC22A8 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Mar 12. Pubmed

4. Solute carrier family 22 member 11

Actions: inhibitor

Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds

UniProt ID: Q9NSA0 Link_out
Gene: SLC22A11 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Mar 12. Pubmed

5. ATP-binding cassette sub-family G member 2

Actions: inhibitor

Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123

UniProt ID: Q9UNQ0 Link_out
Gene: ABCG2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  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. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:45

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.