DrugBank: Fusidic Acid (DB02703)

targets (3) transporters (2)

Identification

Name

Fusidic Acid

Accession Number

DB02703 (EXPT01507)

Type

small molecule

Groups

approved

Description

An antibiotic isolated from the fermentation broth of Fusidium coccineum. (From Merck Index, 11th ed) It acts by inhibiting translocation during protein synthesis.

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Diethanolamine fusidate
Fucidate
Fucidate Sodium
Fucidic acid
Fusidate
Fusidate Sodium

Brand names

Fucidin
Fucidin acid
Fucidin Cream 2%
Fucidine
Fucithalmic
Fusidine
Ramycin

Brand name mixtures

Fucibet (Fusidic acid + betamethasone)
Fucicort (Fusidic acid + hydrocortisone)

Categories

Anti-Bacterial Agents
Protein Synthesis Inhibitors
Antibacterial Agents

CAS number

6990-06-3

Weight

Average: 516.7092
Monoisotopic: 516.345089268

Chemical Formula

C₃₁H₄₈O₆

InChI Key

InChIKey=IECPWNUMDGFDKC-MZJAQBGESA-N

InChI

InChI=1S/C31H48O6/c1-17(2)9-8-10-20(28(35)36)26-22-15-24(34)27-29(5)13-12-23(33)18(3)21(29)11-14-30(27,6)31(22,7)16-25(26)37-19(4)32/h9,18,21-25,27,33-34H,8,10-16H2,1-7H3,(H,35,36)/b26-20-/t18-,21-,22-,23+,24+,25-,27-,29-,30-,31-/m0/s1

Plain Text

IUPAC Name

2-[(1S,2S,5R,6S,7S,10S,11S,13S,14Z,15R,17R)-13-(acetyloxy)-5,17-dihydroxy-2,6,10,11-tetramethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan-14-ylidene]-6-methylhept-5-enoic acid

SMILES

[H][C@@]12C[C@@H](O)[C@@]3([H])[C@@]4(C)CC[C@@H](O)[C@@H](C)[C@]4([H])CC[C@]3(C)[C@@]1(C)C[C@H](OC(C)=O)\C2=C(\CCC=C(C)C)C(O)=O

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Steroids and Steroid Derivatives

Substructures

Steroids and Steroid Derivatives
Carboxylic Acids and Derivatives
Hydroxy Compounds
Alkanes and Alkenes
Acetates
Sterols
Ethers
Bicyclohexanes
Alcohols and Polyols

Pharmacology

Indication

For the treatment of bacterial infections.

Pharmacodynamics

Fusidic acid is a bacteriostatic antibiotic that is often used topically in creams and eyedrops, but may also be given systemically as tablets or injections.

Mechanism of action

Fusidic acid works by interfering with bacterial protein synthesis, specifically by preventing the translocation of the elongation factor G (EF-G) from the ribosome. It also can inhibit chloramphenicol acetyltransferase enzymes.

Absorption

Sodium fusidic acid tablets have a 91% oral bioavailability. Absorption of the film-coated tablets is complete when compared to a solution, however oral absorption is variable. Oral fusidic acid hemihydrate (suspension) achieved a 22.5% bioavailability in pediatric patients following a 20 milligram/kilogram dose.

Volume of distribution

Not Available

Protein binding

97 to 99%

Metabolism

Metabolites include dicarboxylic ester/acid, 3-keto fusidic acid, hydroxy fusidic acid, glucuronide fusidic acid and a glycol metabolite.

Route of elimination

Not Available

Half life

Approximately 5 to 6 hours in adults.

Clearance

Not Available

Toxicity

Not Available

Affected organisms

Enteric bacteria and other eubacteria

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage forms

Not Available

Prices

Unit description	Cost	Unit
Fucidin 2 % Cream	0.66 USD	g
Fucidin 2 % Ointment	0.66 USD	g

Patents

Not Available

Properties

State

solid

Melting point

192.5 oC

Experimental Properties

Not Available

Predicted Properties

Property	Value	Source
water solubility	5.21e-03 g/l	ALOGPS
logP	4.97	ALOGPS
logP	4.42	ChemAxon Molconvert
logS	-5.00	ALOGPS
pKa	18.89	ChemAxon Molconvert
hydrogen acceptor count	5	ChemAxon Molconvert
hydrogen donor count	3	ChemAxon Molconvert
polar surface area	104.06	ChemAxon Molconvert
rotatable bond count	6	ChemAxon Molconvert
refractivity	144.12	ChemAxon Molconvert
polarizability	59.77	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
KEGG Drug	D04281
KEGG Compound	C06694
PubChem Compound	3000226
PubChem Substance	46505364
ChemSpider	2271900
ChEBI	29013
ChEMBL	29013
Therapeutic Targets Database	DAP001008
PharmGKB	PA10087
HET	FUA
Drug Product Database	586668
Wikipedia	http://en.wikipedia.org/wiki/Fusidic_acid

ATC Codes

Not Available

AHFS Codes

Not Available

PDB Entries

1QCA

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Take with food to reduce irritation.

Targets
1. Elongation factor G Pharmacological action: yes Actions: inhibitor This protein promotes the GTP-dependent translocation of the nascent protein chain from the A-site to the P-site of the ribosome Organism class: bacterial UniProt ID: P13551 Gene: fusA Protein Sequence: FASTA SNPs: SNPJam Report References: Lannergard J, Norstrom T, Hughes D: Genetic determinants of resistance to fusidic acid among clinical bacteremia isolates of Staphylococcus aureus. Antimicrob Agents Chemother. 2009 May;53(5):2059-65. Epub 2009 Mar 16. Pubmed Chen Y, Koripella RK, Sanyal S, Selmer M: Staphylococcus aureus elongation factor G—structure and analysis of a target for fusidic acid. FEBS J. 2010 Sep;277(18):3789-803. Pubmed Gao YG, Selmer M, Dunham CM, Weixlbaumer A, Kelley AC, Ramakrishnan V: The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science. 2009 Oct 30;326(5953):694-9. Pubmed 2. Chloramphenicol acetyltransferase Pharmacological action: unknown Actions: inhibitor This enzyme is an effector of chloramphenicol resistance in bacteria Organism class: bacterial UniProt ID: P62580 Gene: cat Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed Murray IA, Cann PA, Day PJ, Derrick JP, Sutcliffe MJ, Shaw WV, Leslie AG: Steroid recognition by chloramphenicol acetyltransferase: engineering and structural analysis of a high affinity fusidic acid binding site. J Mol Biol. 1995 Dec 15;254(5):993-1005. Pubmed Bennett AD, Shaw WV: Resistance to fusidic acid in Escherichia coli mediated by the type I variant of chloramphenicol acetyltransferase. A plasmid-encoded mechanism involving antibiotic binding. Biochem J. 1983 Oct 1;215(1):29-38. Pubmed Day PJ, Murray IA, Shaw WV: Properties of hybrid active sites in oligomeric proteins: kinetic and ligand binding studies with chloramphenicol acetyltransferase trimers. Biochemistry. 1995 May 16;34(19):6416-22. Pubmed 3. Chloramphenicol acetyltransferase 3 Pharmacological action: unknown Actions: inhibitor This enzyme is an effector of chloramphenicol resistance in bacteria Organism class: bacterial UniProt ID: P00484 Gene: cat3 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed Murray IA, Cann PA, Day PJ, Derrick JP, Sutcliffe MJ, Shaw WV, Leslie AG: Steroid recognition by chloramphenicol acetyltransferase: engineering and structural analysis of a high affinity fusidic acid binding site. J Mol Biol. 1995 Dec 15;254(5):993-1005. Pubmed Bennett AD, Shaw WV: Resistance to fusidic acid in Escherichia coli mediated by the type I variant of chloramphenicol acetyltransferase. A plasmid-encoded mechanism involving antibiotic binding. Biochem J. 1983 Oct 1;215(1):29-38. Pubmed Day PJ, Murray IA, Shaw WV: Properties of hybrid active sites in oligomeric proteins: kinetic and ligand binding studies with chloramphenicol acetyltransferase trimers. Biochemistry. 1995 May 16;34(19):6416-22. Pubmed

Targets

1. Elongation factor G

Pharmacological action: yes
Actions: inhibitor

This protein promotes the GTP-dependent translocation of the nascent protein chain from the A-site to the P-site of the ribosome

Organism class: bacterial
UniProt ID: P13551 Link_out

Gene: fusA
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Lannergard J, Norstrom T, Hughes D: Genetic determinants of resistance to fusidic acid among clinical bacteremia isolates of Staphylococcus aureus. Antimicrob Agents Chemother. 2009 May;53(5):2059-65. Epub 2009 Mar 16. Pubmed
Chen Y, Koripella RK, Sanyal S, Selmer M: Staphylococcus aureus elongation factor G—structure and analysis of a target for fusidic acid. FEBS J. 2010 Sep;277(18):3789-803. Pubmed
Gao YG, Selmer M, Dunham CM, Weixlbaumer A, Kelley AC, Ramakrishnan V: The structure of the ribosome with elongation factor G trapped in the posttranslocational state. Science. 2009 Oct 30;326(5953):694-9. Pubmed

2. Chloramphenicol acetyltransferase

Pharmacological action: unknown
Actions: inhibitor

This enzyme is an effector of chloramphenicol resistance in bacteria

Organism class: bacterial
UniProt ID: P62580 Link_out

Gene: cat
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Murray IA, Cann PA, Day PJ, Derrick JP, Sutcliffe MJ, Shaw WV, Leslie AG: Steroid recognition by chloramphenicol acetyltransferase: engineering and structural analysis of a high affinity fusidic acid binding site. J Mol Biol. 1995 Dec 15;254(5):993-1005. Pubmed
Bennett AD, Shaw WV: Resistance to fusidic acid in Escherichia coli mediated by the type I variant of chloramphenicol acetyltransferase. A plasmid-encoded mechanism involving antibiotic binding. Biochem J. 1983 Oct 1;215(1):29-38. Pubmed
Day PJ, Murray IA, Shaw WV: Properties of hybrid active sites in oligomeric proteins: kinetic and ligand binding studies with chloramphenicol acetyltransferase trimers. Biochemistry. 1995 May 16;34(19):6416-22. Pubmed

3. Chloramphenicol acetyltransferase 3

Pharmacological action: unknown
Actions: inhibitor

This enzyme is an effector of chloramphenicol resistance in bacteria

Organism class: bacterial
UniProt ID: P00484 Link_out

Gene: cat3
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Murray IA, Cann PA, Day PJ, Derrick JP, Sutcliffe MJ, Shaw WV, Leslie AG: Steroid recognition by chloramphenicol acetyltransferase: engineering and structural analysis of a high affinity fusidic acid binding site. J Mol Biol. 1995 Dec 15;254(5):993-1005. Pubmed
Bennett AD, Shaw WV: Resistance to fusidic acid in Escherichia coli mediated by the type I variant of chloramphenicol acetyltransferase. A plasmid-encoded mechanism involving antibiotic binding. Biochem J. 1983 Oct 1;215(1):29-38. Pubmed
Day PJ, Murray IA, Shaw WV: Properties of hybrid active sites in oligomeric proteins: kinetic and ligand binding studies with chloramphenicol acetyltransferase trimers. Biochemistry. 1995 May 16;34(19):6416-22. 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 Gene: ABCB11 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Bode KA, Donner MG, Leier I, Keppler D: Inhibition of transport across the hepatocyte canalicular membrane by the antibiotic fusidate. Biochem Pharmacol. 2002 Jul 1;64(1):151-8. Pubmed 2. Canalicular multispecific organic anion transporter 1 Actions: inhibitor Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter UniProt ID: Q92887 Gene: ABCC2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Bode KA, Donner MG, Leier I, Keppler D: Inhibition of transport across the hepatocyte canalicular membrane by the antibiotic fusidate. Biochem Pharmacol. 2002 Jul 1;64(1):151-8. 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:

Bode KA, Donner MG, Leier I, Keppler D: Inhibition of transport across the hepatocyte canalicular membrane by the antibiotic fusidate. Biochem Pharmacol. 2002 Jul 1;64(1):151-8. Pubmed

2. Canalicular multispecific organic anion transporter 1

Actions: inhibitor

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out

Gene: ABCC2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Bode KA, Donner MG, Leier I, Keppler D: Inhibition of transport across the hepatocyte canalicular membrane by the antibiotic fusidate. Biochem Pharmacol. 2002 Jul 1;64(1):151-8. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:11

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.