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

Details

Stereochemistry ABSOLUTE
Molecular Formula C12H15N5O3.C4H4O4
Molecular Weight 393.352
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of ENTECAVIR MALEATE

SMILES

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

InChI

InChIKey=UEXBBJAYBDAHLG-FJESMAGSSA-N
InChI=1S/C12H15N5O3.C4H4O4/c1-5-6(3-18)8(19)2-7(5)17-4-14-9-10(17)15-12(13)16-11(9)20;5-3(6)1-2-4(7)8/h4,6-8,18-19H,1-3H2,(H3,13,15,16,20);1-2H,(H,5,6)(H,7,8)/b;2-1-/t6-,7-,8-;/m0./s1

HIDE SMILES / InChI

Molecular Formula C4H4O4
Molecular Weight 116.0723
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

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
[Entecavir therapy against hepatitis B].
2004 Aug
[Treatment and selection criteria for chronic hepatitis B].
2004 Aug
[Recent advances in the treatment of fulminant hepatitis B].
2004 Aug
[Advances in the treatment of acute 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
Emerging treatments in chronic hepatitis B.
2004 Nov
[Treatment of hepatitis B].
2004 Nov 7
Gateways to clinical trials.
2004 Sep
Cross-resistance testing of next-generation nucleoside and nucleotide analogues against lamivudine-resistant HBV.
2005
Management of HBV/HIV-coinfected Patients.
2005
Clinical trial results of new therapies for HBV: implications for treatment guidelines.
2005
Current treatment of chronic hepatitis B: benefits and limitations.
2005
Drugs in development for hepatitis B.
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
Hepatitis B virus infection: current status.
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
Gateways to clinical trials.
2005 Jan-Feb
FDA notifications. Entecavir is approved for chronic hepatitis B infection in adults.
2005 Jul
Chronic hepatitis B--treatment with nucleoside analogues.
2005 Jul
Entecavir.
2005 Jul
[A study of the dosage and efficacy of entecavir for treating hepatitis B virus].
2005 Jul
Treatment of chronic hepatitis B.
2005 Jul
New treatment for chronic hepatitis B.
2005 Jul-Aug
Clinical course of patients with chronic hepatitis B with viral breakthrough during long-term lamivudine treatment.
2005 Jun
Management of patients co-infected with hepatitis B virus and HIV.
2005 Jun
Susceptibility to antivirals of a human HBV strain with mutations conferring resistance to both lamivudine and adefovir.
2005 Jun
Entecavir (Baraclude) for chronic hepatitis B.
2005 Jun 6
Current and future treatment of chronic hepatitis B.
2005 Mar
[Treatment of chronic hepatitis B].
2005 Mar 31
Gateways to clinical trials.
2005 May
New drugs and dosage forms.
2005 May 1
New drugs: entecavir, ibandronate sodium, and pegaptanib sodium.
2005 May-Jun
Gateways to clinical trials.
2005 Nov
A review of entecavir in the treatment of chronic hepatitis B infection.
2005 Nov
A dose-ranging study of the efficacy and tolerability of entecavir in Lamivudine-refractory chronic hepatitis B patients.
2005 Oct
Clevudine for the treatment of chronic hepatitis B virus infection.
2005 Oct
Natural history and treatment of hepatitis B virus and hepatitis C virus coinfection.
2005 Sep 13
[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
Introduction to chronic hepatitis B infection.
2006
Emerging therapeutics for chronic hepatitis B.
2006
Treatment algorithm for chronic hepatitis B in HIV-infected patients.
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 02:33:48 UTC 2021
Edited
by admin
on Sat Jun 26 02:33:48 UTC 2021
Record UNII
92A92XBK4S
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ENTECAVIR MALEATE
Common Name English
6H-PURIN-6-ONE, 2-AMINO-1,9-DIHYDRO-9-((1S,3R,4S)-4-HYDROXY-3-(HYDROXYMETHYL)-2-METHYLENECYCLOPENTYL)-, (2Z)-2-BUTENEDIOATE (1:1)
Systematic Name English
ENTECAVIR MALEATE [WHO-DD]
Common Name English
Code System Code Type Description
FDA UNII
92A92XBK4S
Created by admin on Sat Jun 26 02:33:48 UTC 2021 , Edited by admin on Sat Jun 26 02:33:48 UTC 2021
PRIMARY
CAS
911138-73-3
Created by admin on Sat Jun 26 02:33:48 UTC 2021 , Edited by admin on Sat Jun 26 02:33:48 UTC 2021
PRIMARY
PUBCHEM
135449303
Created by admin on Sat Jun 26 02:33:48 UTC 2021 , Edited by admin on Sat Jun 26 02:33:48 UTC 2021
PRIMARY
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