U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C12H15N5O3
Molecular Weight 277.2797
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ENTECAVIR ANHYDROUS

SMILES

C=C1[C@]([H])(CO)[C@]([H])(C[C@]1([H])n2cnc3c2[nH]c(=N)nc3O)O

InChI

InChIKey=QDGZDCVAUDNJFG-FXQIFTODSA-N
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

HIDE SMILES / InChI

Molecular Formula C12H15N5O3
Molecular Weight 277.2797
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: Description was created based on several resourses, including http://www.drugs.com/monograph/entecavir.html and http://www.drugbank.ca/drugs/DB00442

BARACLUDE® is the tradename for entecavir, a guanosine nucleoside analogue with selective activity against hepatitis B virus (HBV). It inhibits all three steps in the viral replication process. 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. Entecavir is used 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.

CNS Activity

Curator's Comment:: Low concentrations of entecavir were found in the cerebrospinal fluid of mice, rats, dogs and monkeys indicating that entecavir can cross the blood brain barrier.

Originator

Curator's Comment:: # Bristol-Myers Squibb Pharmaceutical Co.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: CHEMBL2311221
0.004 µM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Entecavir

Approved Use

BARACLUDE (entecavir) is indicated 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.

Launch Date

1.11205443E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
4.23 ng/mL
0.5 mg 1 times / day steady-state, oral
dose: 0.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ENTECAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
8.24 ng/mL
1 mg 1 times / day steady-state, oral
dose: 1 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ENTECAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
8.1 ng/mL
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ENTECAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
4.2 ng/mL
0.5 mg 1 times / day steady-state, oral
dose: 0.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ENTECAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
14.78 ng × h/mL
0.5 mg 1 times / day steady-state, oral
dose: 0.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ENTECAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
26.38 ng × h/mL
1 mg 1 times / day steady-state, oral
dose: 1 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ENTECAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
27.9 ng × h/mL
1 mg single, oral
dose: 1 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ENTECAVIR plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
129.9 h
0.5 mg 1 times / day steady-state, oral
dose: 0.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ENTECAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
148.89 h
1 mg 1 times / day steady-state, oral
dose: 1 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ENTECAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
138.5 h
0.5 mg 1 times / day steady-state, oral
dose: 0.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ENTECAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
87%
0.5 mg 1 times / day steady-state, oral
dose: 0.5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
ENTECAVIR plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1 mg 1 times / day steady, oral
Highest studied dose
Dose: 1 mg, 1 times / day
Route: oral
Route: steady
Dose: 1 mg, 1 times / day
Sources: Page: 6.1
unhealthy, adult
n = 183
Health Status: unhealthy
Condition: hepatitis B
Age Group: adult
Sex: unknown
Population Size: 183
Sources: Page: 6.1
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive
no [IC50 >300 uM]
no (co-administration study)
Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with phenacetin
Page: 42, 154, 155
no [IC50 >300 uM]
no (co-administration study)
Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with S-mephentytoin
Page: 42, 154, 155
no [IC50 >300 uM]
no (co-administration study)
Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with S-mephentytoin
Page: 42, 154, 155
no [IC50 >300 uM]
no (co-administration study)
Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with diclofenac
Page: 42, 154, 155
no [IC50 >300 uM]
no (co-administration study)
Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with bufuralol
Page: 42, 154, 155
no [IC50 >300 uM]
no (co-administration study)
Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with p-nitrophenol
Page: 42, 154, 155
no [IC50 >300 uM]
no (co-administration study)
Comment: at clinically relevant concentrations entecavir inhibitied catalytic activities no greater than 9% with testosterone
Page: 42, 154, 155
no
no
no
no
no
no
no
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Perspectives for the treatment of hepatitis B virus infections.
1999 Jul
[Hepatitis B in children: natural history and therapy].
2001
Detection of hepatitis B virus resistance to antivirals.
2001 Jun
Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection.
2001 Sep
Treatment of chronic hepatitis B: case selection and duration of therapy.
2002 Apr
Management of patients with chronic hepatitis B.
2002 Apr
Combination and newer therapies for chronic hepatitis B.
2002 Dec
Entecavir is superior to lamivudine in reducing hepatitis B virus DNA in patients with chronic hepatitis B infection.
2002 Dec
Management of viral hepatitis B.
2002 Feb
Chronic hepatitis B: current and future treatment options.
2002 Jun
Gateways to clinical trials.
2002 Oct
Entecavir, FTC, L-FMAU, LdT and others.
2003
Characterization of antiviral activity of entecavir in transgenic mice expressing hepatitis B virus.
2003 Aug
[Nucleoside analogues resistance in the treatment of chronic hepatitis B virus infection].
2003 Dec
[Antiviral therapy for chronic viral hepatitis B and C].
2003 Feb
Management of patients with decompensated HBV cirrhosis.
2003 Feb
Treatment of HBeAg-negative chronic hepatitis B.
2003 Feb
In vitro activity of potential anti-poxvirus agents.
2003 Jan
Gateways to clinical trials.
2003 Jan-Feb
Current and future antiviral agents for chronic hepatitis B.
2003 Mar
Prevention of and treatment for hepatitis B virus infection after liver transplantation in the nucleoside analogues era.
2003 Mar
Gateways to clinical trials.
2003 Oct
Doctor to patient transmission of hepatitis B virus: implications of HBV DNA levels and potential new solutions.
2003 Oct
Gateways to clinical trials.
2003 Sep
[Recent advances in the treatment of fulminant hepatitis B].
2004 Aug
Management of hepatitis B patients with antiviral resistance.
2004 Dec
Entecavir for the treatment of chronic hepatitis B.
2004 Dec
Gateways to clinical trials.
2004 Nov
Gateways to clinical trials.
2004 Sep
Cross-resistance testing of next-generation nucleoside and nucleotide analogues against lamivudine-resistant HBV.
2005
The current status of antiviral therapy of chronic hepatitis B.
2005 Dec
Complications in treating chronic hepatitis B in patients with HIV.
2005 Dec
Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation.
2005 Dec
Entecavir.
2005 Jul
[A study of the dosage and efficacy of entecavir for treating hepatitis B virus].
2005 Jul
Susceptibility to antivirals of a human HBV strain with mutations conferring resistance to both lamivudine and adefovir.
2005 Jun
New drugs and dosage forms.
2005 May 1
Gateways to clinical trials.
2005 Nov
Clevudine for the treatment of chronic hepatitis B virus infection.
2005 Oct
[New aspect in the treatment of chronic hepatis B].
2005 Sep 7
Optimizing management strategies in special patient populations.
2006
Looking to the future: new agents for chronic hepatitis B.
2006
Therapeutic options for chronic hepatitis B: considerations and controversies.
2006
Cellular and virological mechanisms of HBV drug resistance.
2006 Feb
Patents

Patents

Sample Use Guides

Nucleoside-naive Individuals Oral 0.5 mg once daily. Lamivudine-refractory HBV or known lamivudine- or telbivudine-associated resistance mutations Oral 1 mg once daily
Route of Administration: Oral
Dendritic cells (DCs) derived from chronic hepatitis B (CHB) patients were treated with 0.05 ug/mL of Entecavir.
Substance Class Chemical
Created
by admin
on Sat Jun 26 05:10:37 UTC 2021
Edited
by admin
on Sat Jun 26 05:10:37 UTC 2021
Record UNII
NNU2O4609D
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ENTECAVIR ANHYDROUS
Common Name English
2-AMINO-9-((1S,3R,4S)-4-HYDROXY-3-(HYDROXYMETHYL)-2-METHYLENECYCLOPENTYL)-1,9-DIHYDRO-6H-PURIN-6-ONE
Systematic Name English
ANHYDROUS ENTECAVIR
Common Name English
ENTECAVIR [MI]
Common Name English
ENTECAVIR [WHO-DD]
Common Name English
6H-PURIN-6-ONE, 2-AMINO-1,9-DIHYDRO-9-((1S,3R,4S)-4-HYDROXY-3-(HYDROXYMETHYL)-2-METHYLENECYCLOPENTYL)-
Systematic Name English
ENTECAVIR [HSDB]
Common Name English
ENTECAVIR [INN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C97452
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
NDF-RT N0000175459
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
NDF-RT N0000175459
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
NDF-RT N0000175656
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
WHO-ATC J05AF10
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
NDF-RT N0000009947
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
NDF-RT N0000175459
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C76494
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
PRIMARY
HSDB
7334
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
PRIMARY
CAS
142217-69-4
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
PRIMARY
EVMPD
SUB25418
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
PRIMARY
PUBCHEM
135398508
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
PRIMARY
MERCK INDEX
M4919
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
PRIMARY Merck Index
DRUG BANK
DB00442
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
PRIMARY
EPA CompTox
142217-69-4
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
PRIMARY
RXCUI
1546027
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
PRIMARY RxNorm
EVMPD
SUB21468
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
PRIMARY
FDA UNII
NNU2O4609D
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
PRIMARY
INN
7904
Created by admin on Sat Jun 26 05:10:38 UTC 2021 , Edited by admin on Sat Jun 26 05:10:38 UTC 2021
PRIMARY
Related Record Type Details
TARGET ORGANISM->INHIBITOR
EC50
BINDER->LIGAND
BINDING
EXCRETED UNCHANGED
MAJOR
URINE
SALT/SOLVATE -> PARENT
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

SINGLE DOSE