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Identification
Name Entecavir
Accession Number DB00442 (APRD00948)
Type small molecule
Groups approved
Description

Entecavir is an oral antiviral drug used in the treatment of hepatitis B infection. It is marketed under the trade name Baraclude (BMS).

Entecavir is a guanine analogue that inhibits all three steps in the viral replication process, and the manufacturer claims that it is more efficacious than previous agents used to treat hepatitis B (lamivudine and adefovir). It was approved by the U.S. Food and Drug Administration (FDA) in March 2005.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • entecavir
Brand names
  • Baraclude
Brand name mixtures Not Available
Categories
  • Antiviral Agents
CAS number 142217-69-4
Weight Average: 277.2792
Monoisotopic: 277.117489371
Chemical Formula C12H15N5O3
InChI Key InChIKey=QDGZDCVAUDNJFG-FXQIFTODSA-N
InChI
InChI=1S/C12H15N5O3/c1-5-6(3-18)8(19)2-7(5)17-4-14-9-10(17)15-12(13)16-11(9)20/h4,6-8,18-19H,1-3H2,(H3,13,15,16,20)/t6-,7-,8-/m0/s1
Plain Text
IUPAC Name
2-amino-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylidenecyclopentyl]-6,9-dihydro-3H-purin-6-one
SMILES
NC1=NC(=O)C2=C(N1)N(C=N2)[C@H]1C[C@H](O)[C@@H](CO)C1=C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Hypoxanthines
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Aliphatic and Aryl Amines
  • Alcohols and Polyols
  • Pyrimidines and Derivatives
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Cyanamides
  • Hypoxanthines
Pharmacology
Indication For the treatment of chronic hepatitis B virus infection in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
Pharmacodynamics Entecavir is a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). It is designed to selectively inhibit the Hepatitis B virus, blocking all three steps in the replication process. Entecavir is more efficient than an older Hepatitis B drug, lamivudine.
Mechanism of action By competing with the natural substrate deoxyguanosine triphosphate, entecavir functionally inhibits all three activities of the HBV polymerase (reverse transcriptase, rt): (1) base priming, (2) reverse transcription of the negative strand from the pregenomic messenger RNA, and (3) synthesis of the positive strand of HBV DNA. Upon activation by kinases, the drug can be incorporated into the DNA which has the ultimate effect of inhibiting the HBV polymerase activity.
Absorption Absorption Following oral administration in healthy subjects, entecavir peak plasma concentrations occurred between 0.5 and 1.5 hours. In healthy subjects, the bioavailability of the tablet is 100% relative to the oral solution.
Volume of distribution Not Available
Protein binding Binding of entecavir to human serum proteins in vitro is approximately 13%.
Metabolism

Entecavir is not a substrate, inhibitor, or inducer of the cytochrome P450 (CYP450) enzyme system. Entecavir is efficiently phosphorylated to the active triphosphate form.
Route of elimination Not Available
Half life After reaching peak concentration, entecavir plasma concentrations decreased in a bi-exponential manner with a terminal elimination half-life of approximately 128-149 hours. The phosphorylated metabolite has a half-life of 15 hours.
Clearance
  • renal cl=383.2 +/- 101.8 mL/min [Unimpaired renal function]
  • renal cl=197.9 +/- 78.1 mL/min [Mild impaired renal function]
  • renal cl=135.6 +/- 31.6 mL/min [Moderate impaired renal function]
  • renal cl=40.3 +/- 10.1 mL/min [severe impaired renal function]
  • apparent oral cl=588.1 +/- 153.7 mL/min [Unimpaired renal function]
  • apparent oral cl=309.2 +/- 62.6 mL/min [Mild impaired renal function]
  • apparent oral cl=226.3 +/- 60.1 mL/min [Moderate impaired renal function]
  • apparent oral cl=100.6 +/- 29.1 mL/min [severe impaired renal function]
  • apparent oral cl=50.6 +/- 16.5 mL/min [severe impaired renal function amnaged with Hemodialysis]
  • apparent oral cl=35.7 +/- 19.6 mL/min [severe impaired renal function amnaged with CAPD]
Toxicity Healthy subjects who received single entecavir doses up to 40 mg or multiple doses up to 20 mg/day for up to 14 days had no increase in or unexpected adverse events. If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.
Affected organisms
  • Hepatitis B virus
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Bristol myers squibb
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Baraclude 0.5 mg tablet 28.94 USD tablet
Baraclude 1 mg tablet 28.94 USD tablet
Patents
Country Patent Number Approved Expires
United States 5206244 1995-02-21 2015-02-21
Canada 2053339 2001-05-29 2011-10-11
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility Slightly soluble (2.4 mg/mL at pH 7.9, 25oC) PhysProp
logP -0.8 PhysProp
Predicted Properties
Property Value Source
water solubility 6.59e+00 g/l ALOGPS
logP -0.81 ALOGPS
logP -1.44 ChemAxon Molconvert
logS -1.62 ALOGPS
pKa 14.64 ChemAxon Molconvert
hydrogen acceptor count 7 ChemAxon Molconvert
hydrogen donor count 4 ChemAxon Molconvert
polar surface area 125.76 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 71.00 ChemAxon Molconvert
polarizability 27.31 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D04008 Link_out
PubChem Compound 153941 Link_out
PubChem Substance 46504864 Link_out
ChemSpider 135679 Link_out
Therapeutic Targets Database DAP000697 Link_out
Drug Product Database 2282224 Link_out
RxList http://www.rxlist.com/cgi/generic4/baraclude.htm Link_out
Drugs.com http://www.drugs.com/cdi/entecavir.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Entecavir Link_out
ATC Codes
  • J05AF10
AHFS Codes
  • 08:18.32
PDB Entries Not Available
FDA label show (628.1 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Food Interactions
  • Take on an empty stomach.
  • Taking the product with a high-fat meal or a light snack reduces the maximal concentration by 44 to 46% and total exposure by 18 to 20%.
Targets

1. DNA

Pharmacological action: yes
Actions: other

DNA is the molecule of heredity, as it is responsible for the genetic propagation of most inherited traits. It is a polynucleic acid that carries genetic information on cell growth, division, and function. DNA consists of two long strands of nucleotides twisted into a double helix and held together by hydrogen bonds. The sequence of nucleotides determines hereditary characteristics. Each strand serves as the template for subsequent DNA replication and as a template for mRNA production, leading to protein synthesis via ribosomes.

Gene Sequence: FASTA

References:
  1. Sims KA, Woodland AM: Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection. Pharmacotherapy. 2006 Dec;26(12):1745-57. Pubmed
  2. Walsh AW, Langley DR, Colonno RJ, Tenney DJ: Mechanistic characterization and molecular modeling of hepatitis B virus polymerase resistance to entecavir. PLoS One. 2010 Feb 12;5(2):e9195. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:39

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.