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 Date2005 |
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 |
|
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 |
|
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 |
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 |
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 |
|---|---|---|
| Cellular and virological mechanisms of HBV drug resistance. | 2006-02 |
|
| 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 |
|
| The current status of antiviral therapy of chronic hepatitis B. | 2005-12 |
|
| Hepatitis B virus infection: current status. | 2005-12 |
|
| Complications in treating chronic hepatitis B in patients with HIV. | 2005-12 |
|
| Adefovir-resistant hepatitis B can be associated with viral rebound and hepatic decompensation. | 2005-12 |
|
| Gateways to clinical trials. | 2005-11 |
|
| A review of entecavir in the treatment of chronic hepatitis B infection. | 2005-11 |
|
| New treatment for chronic hepatitis B. | 2005-10-29 |
|
| A dose-ranging study of the efficacy and tolerability of entecavir in Lamivudine-refractory chronic hepatitis B patients. | 2005-10 |
|
| Clevudine for the treatment of chronic hepatitis B virus infection. | 2005-10 |
|
| Natural history and treatment of hepatitis B virus and hepatitis C virus coinfection. | 2005-09-13 |
|
| [New aspect in the treatment of chronic hepatis B]. | 2005-09-07 |
|
| Managing hepatitis B coinfection in HIV-infected patients. | 2005-08 |
|
| New drugs: entecavir, ibandronate sodium, and pegaptanib sodium. | 2005-07-05 |
|
| FDA notifications. Entecavir is approved for chronic hepatitis B infection in adults. | 2005-07 |
|
| Chronic hepatitis B--treatment with nucleoside analogues. | 2005-07 |
|
| Entecavir. | 2005-07 |
|
| [A study of the dosage and efficacy of entecavir for treating hepatitis B virus]. | 2005-07 |
|
| Treatment of chronic hepatitis B. | 2005-07 |
|
| Entecavir (Baraclude) for chronic hepatitis B. | 2005-06-06 |
|
| Clinical course of patients with chronic hepatitis B with viral breakthrough during long-term lamivudine treatment. | 2005-06 |
|
| Management of patients co-infected with hepatitis B virus and HIV. | 2005-06 |
|
| Susceptibility to antivirals of a human HBV strain with mutations conferring resistance to both lamivudine and adefovir. | 2005-06 |
|
| New drugs and dosage forms. | 2005-05-01 |
|
| Gateways to clinical trials. | 2005-05 |
|
| Gateways to clinical trials. | 2005-04-19 |
|
| US approves new HBV drug. | 2005-04 |
|
| [Treatment of chronic hepatitis B]. | 2005-03-31 |
|
| Current and future treatment of chronic hepatitis B. | 2005-03 |
|
| 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 |
|
| Management of hepatitis B patients with antiviral resistance. | 2004-12 |
|
| Entecavir for the treatment of chronic hepatitis B. | 2004-12 |
|
| [Treatment of hepatitis B]. | 2004-11-07 |
|
| Gateways to clinical trials. | 2004-11 |
|
| Emerging treatments in chronic hepatitis B. | 2004-11 |
|
| Gateways to clinical trials. | 2004-09 |
|
| [Entecavir therapy against hepatitis B]. | 2004-08 |
|
| [Treatment and selection criteria for chronic hepatitis B]. | 2004-08 |
|
| [Recent advances in the treatment of fulminant hepatitis B]. | 2004-08 |
|
| [Advances in the treatment of acute hepatitis B]. | 2004-08 |
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
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NNU2O4609D
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J05AF10
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N0000009947
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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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ACTIVE MOIETY |
| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
|---|---|---|---|---|---|---|
| Tmax | PHARMACOKINETIC |
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ORAL ADMINISTRATION |
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