Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C12H15N5O3 |
Molecular Weight | 277.2792 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=NC2=C(N=CN2[C@H]3C[C@H](O)[C@@H](CO)C3=C)C(=O)N1
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
Molecular Formula | C12H15N5O3 |
Molecular Weight | 277.2792 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 3 / 3 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
DescriptionCurator's Comment: Description was created based on several resourses, including http://www.drugs.com/monograph/entecavir.html and http://www.drugbank.ca/drugs/DB00442
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
Sources: http://www.hc-sc.gc.ca/dhp-mps/alt_formats/hpfb-dgpsa/pdf/prodpharma/sbd_smd_2007_baraclude_102555-eng.pdf
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.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2311221 Sources: http://www.drugbank.ca/drugs/DB00442 |
0.004 µM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Entecavir Approved UseBARACLUDE (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 Date1.11205443E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
4.23 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17050790/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17050790/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
14.78 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17050790/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17050790/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
129.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17050790/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17050790/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Dose | Population | Adverse 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 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 42.0 |
inconclusive | |||
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 phenacetin Page: 42, 154, 155 |
||
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 |
||
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 |
||
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 |
||
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 |
||
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 |
||
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 |
||
Page: 4, 16 |
no | |||
Page: 4, 16 |
no | |||
Page: 17.0 |
no | |||
Page: 17.0 |
no | |||
Page: 17.0 |
no | |||
Page: 17.0 |
no | |||
Page: 17.0 |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 46.0 |
likely | |||
Page: 4, 16 |
no | |||
Page: 5.0 |
no | |||
yes | ||||
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 12, 13, 14 |
PubMed
Title | Date | PubMed |
---|---|---|
Perspectives for the treatment of hepatitis B virus infections. | 1999 Jul |
|
Antiviral drugs: current state of the art. | 2001 Aug |
|
Entecavir (Bristol-Myers Squibb). | 2001 May |
|
Efficacies of entecavir against lamivudine-resistant hepatitis B virus replication and recombinant polymerases in vitro. | 2002 Aug |
|
Combination and newer therapies for chronic hepatitis B. | 2002 Dec |
|
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 |
|
[New management strategies for hepatitis B]. | 2002 Feb |
|
Potent efficacy of entecavir (BMS-200475) in a duck model of hepatitis B virus replication. | 2002 Jan |
|
Viral dynamics during and after entecavir therapy in patients with chronic hepatitis B. | 2002 Jul |
|
Therapy of chronic hepatitis B: current challenges and opportunities. | 2002 Nov |
|
Gateways to clinical trials. | 2002 Oct |
|
Treatment of HBeAg-negative chronic hepatitis B. | 2003 Feb |
|
Current and future antiviral agents for chronic hepatitis B. | 2003 Mar |
|
Gateways to clinical trials. | 2003 Sep |
|
New treatment of chronic hepatitis B. | 2004 |
|
Editorial comment: HIV and HBV coinfection--a coming-of-age in treatment strategies. | 2004 Mar |
|
Hepatitis B virus epidemiology, disease burden, treatment, and current and emerging prevention and control measures. | 2004 Mar |
|
Combinations of adefovir with nucleoside analogs produce additive antiviral effects against hepatitis B virus in vitro. | 2004 Oct |
|
Gateways to clinical trials. | 2004 Sep |
|
Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to Lamivudine. | 2004 Sep |
|
The current status of antiviral therapy of chronic hepatitis B. | 2005 Dec |
|
Gateways to clinical trials. | 2005 Jan-Feb |
|
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 |
|
Entecavir (Baraclude) for chronic hepatitis B. | 2005 Jun 6 |
|
Gateways to clinical trials. | 2005 May |
|
Gateways to clinical trials. | 2005 Nov |
|
A review of entecavir in the treatment of chronic hepatitis B infection. | 2005 Nov |
|
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 |
|
Treatment algorithm for chronic hepatitis B in HIV-infected patients. | 2006 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: http://www.drugs.com/monograph/entecavir.html
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
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/?term=18330958
Dendritic cells (DCs) derived from chronic hepatitis B (CHB) patients were treated with 0.05 ug/mL of Entecavir.
Substance Class |
Chemical
Created
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admin
on
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Wed Jul 05 23:12:51 UTC 2023
by
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on
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Record UNII |
NNU2O4609D
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Record Status |
Validated (UNII)
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C97452
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J05AF10
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DB00442
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Related Record | Type | Details | ||
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SOLVATE->ANHYDROUS | |||
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TARGET ORGANISM->INHIBITOR |
EC50
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BINDER->LIGAND |
BINDING
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EXCRETED UNCHANGED |
MAJOR
URINE
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SALT/SOLVATE -> PARENT | |||
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SALT/SOLVATE -> PARENT |
Related Record | Type | Details | ||
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METABOLITE -> PARENT |
PLASMA; URINE
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Tmax | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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