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

Details

Stereochemistry ABSOLUTE
Molecular Formula C12H15N5O3.H2O
Molecular Weight 295.2945
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ENTECAVIR

SMILES

O.NC1=NC2=C(N=CN2[C@H]3C[C@H](O)[C@@H](CO)C3=C)C(=O)N1

InChI

InChIKey=YXPVEXCTPGULBZ-WQYNNSOESA-N
InChI=1S/C12H15N5O3.H2O/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);1H2/t6-,7-,8-;/m0./s1

HIDE SMILES / InChI

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

2005
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
[Hepatitis B in children: natural history and therapy].
2001
Current pharmacotherapy for hepatitis B infection.
2001 Aug
Antiviral drugs: current state of the art.
2001 Aug
Nucleoside analogues for chronic hepatitis B.
2001 Dec
Treatment of chronic hepatitis B.
2001 Nov
Safety and efficacy of oral entecavir given for 28 days in patients with chronic hepatitis B virus infection.
2001 Sep
Management of YMDD mutations during lamivudine therapy in patients with 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
Nucleoside analogues for chronic hepatitis B: antiviral efficacy and viral resistance.
2002 Jul
Therapy of chronic hepatitis B: current challenges and opportunities.
2002 Nov
Gateways to clinical trials.
2002 Oct
Prevention of recurrent hepatitis B post-liver transplantation.
2002 Oct
Entecavir: a potent new antiviral drug for hepatitis B.
2003 Apr
Selection of a hepatitis B virus strain resistant to adefovir in a liver transplantation patient.
2003 Dec
In vitro activity of potential anti-poxvirus agents.
2003 Jan
Gateways to clinical trials.
2003 Jan-Feb
Prevention of and treatment for hepatitis B virus infection after liver transplantation in the nucleoside analogues era.
2003 Mar
Doctor to patient transmission of hepatitis B virus: implications of HBV DNA levels and potential new solutions.
2003 Oct
[Entecavir therapy against hepatitis B].
2004 Aug
Management of hepatitis B patients with antiviral resistance.
2004 Dec
[New approaches in the treatment of hepatitis B].
2004 May 21
Gateways to clinical trials.
2004 Nov
Gateways to clinical trials.
2004 Sep
Management of HBV/HIV-coinfected Patients.
2005
Current treatment of chronic hepatitis B: benefits and limitations.
2005
US approves new HBV drug.
2005 Apr
Managing hepatitis B coinfection in HIV-infected patients.
2005 Aug
The current status of antiviral therapy of chronic hepatitis B.
2005 Dec
Chronic hepatitis B--treatment with nucleoside analogues.
2005 Jul
Management of patients co-infected with hepatitis B virus and HIV.
2005 Jun
Entecavir (Baraclude) for chronic hepatitis B.
2005 Jun 6
[Treatment of chronic hepatitis B].
2005 Mar 31
New drugs and dosage forms.
2005 May 1
New drugs: entecavir, ibandronate sodium, and pegaptanib sodium.
2005 May-Jun
Optimizing management strategies in special patient populations.
2006
Looking to the future: new agents for chronic hepatitis B.
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.
Name Type Language
ENTECAVIR
EMA EPAR   MART.   ORANGE BOOK   USAN   VANDF  
USAN  
Official Name English
SQ-34676
Code English
ENTECAVIR MONOHYDRATE [USP-RS]
Common Name English
ENTECAVIR MONOHYDRATE
MI   USP-RS   WHO-DD  
Common Name English
ENTECAVIR [USP MONOGRAPH]
Common Name English
9-[(1S,3R,4S)-4-Hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]guanine monohydrate
Systematic Name English
ENTECAVIR [USAN]
Common Name English
ENTECAVIR [ORANGE BOOK]
Common Name English
ENTECAVIR MONOHYDRATE [MI]
Common Name English
ENTECAVIR HYDRATE
JAN  
Common Name English
6H-PURIN-6-ONE, 2-AMINO-1,9-DIHYDRO-9-((1S,3R,4S)-4-HYDROXY-3-(HYDROXYMETHYL)-2-METHYLENECYCLOPENTYL)- MONOHYDRATE
Systematic Name English
ENTECAVIR MONOHYDRATE [EP MONOGRAPH]
Common Name English
Entecavir monohydrate [WHO-DD]
Common Name English
BARACLUDE
Brand Name English
SQ34676
Code English
ENTECAVIR [EMA EPAR]
Common Name English
BMS-200475-01
Code English
ENTECAVIR [VANDF]
Common Name English
ENTECAVIR HYDRATE [JAN]
Common Name English
ENTECAVIR [MART.]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C97452
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
WHO-VATC QJ05AF10
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
WHO-ATC J05AF10
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
LIVERTOX NBK548075
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
EMA ASSESSMENT REPORTS BARACLUDE (AUTHORIZED: HEPATITIS B, CHRONIC)
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
NDF-RT N0000175656
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
Code System Code Type Description
CAS
209216-23-9
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
PRIMARY
EPA CompTox
DTXSID00943185
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PRIMARY
ChEMBL
CHEMBL713
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PRIMARY
RXCUI
306266
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PRIMARY RxNorm
DRUG BANK
DB00442
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
PRIMARY
SMS_ID
100000089463
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PRIMARY
FDA UNII
5968Y6H45M
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
PRIMARY
WIKIPEDIA
ENTECAVIR
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
PRIMARY
PUBCHEM
135526609
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PRIMARY
DAILYMED
5968Y6H45M
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
PRIMARY
LACTMED
Entecavir
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
PRIMARY
DRUG CENTRAL
1019
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
PRIMARY
MESH
C413685
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PRIMARY
EVMPD
SUB25434
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PRIMARY
RS_ITEM_NUM
1235966
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PRIMARY
NCI_THESAURUS
C65513
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
PRIMARY
USAN
KK-110
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PRIMARY
CHEBI
473990
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
PRIMARY
MERCK INDEX
m4919
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
PRIMARY Merck Index
CHEBI
59902
Created by admin on Fri Dec 15 16:10:08 GMT 2023 , Edited by admin on Fri Dec 15 16:10:08 GMT 2023
PRIMARY