Details
Stereochemistry | ACHIRAL |
Molecular Formula | C8H12N5O4P |
Molecular Weight | 273.1857 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
NC1=NC=NC2=C1N=CN2CCOCP(O)(O)=O
InChI
InChIKey=SUPKOOSCJHTBAH-UHFFFAOYSA-N
InChI=1S/C8H12N5O4P/c9-7-6-8(11-3-10-7)13(4-12-6)1-2-17-5-18(14,15)16/h3-4H,1-2,5H2,(H2,9,10,11)(H2,14,15,16)
DescriptionCurator's Comment: Description was created based on several sources, including:
https://www.ncbi.nlm.nih.gov/pubmed/14498759
http://link.springer.com/chapter/10.1007%2F978-0-387-49785-3_33
Curator's Comment: Description was created based on several sources, including:
https://www.ncbi.nlm.nih.gov/pubmed/14498759
http://link.springer.com/chapter/10.1007%2F978-0-387-49785-3_33
The potential antiviral effect of adefovir, an acyclic nucleoside phosphonate analog of 2′-deoxyadenosine monophosphate, was first studied by Holý and De Clercq in 1980s.
Adefovir is an acyclic nucleotide analog of adenosine monophosphate which is phosphorylated to the active metabolite adefovir diphosphate by cellular kinases. Adefovir diphosphate inhibits HBV DNA polymerase (reverse transcriptase) by competing with the natural substrate deoxyadenosine triphosphate and by causing DNA chain termination after its incorporation into viral DNA. Oral adefovir dipivoxil is effective and generally well tolerated in HBeAg-positive and -negative patients chronically infected with wild-type or lamivudine-resistant HBV.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL1743128 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23956101 |
133.0 µM [IC50] | ||
Target ID: CHEMBL6020 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23956101 |
46.0 µM [IC50] | ||
Target ID: CHEMBL5748 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23956101 |
133.0 µM [IC50] | ||
Target ID: CHEMBL5918 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23956101 |
133.0 µM [IC50] | ||
Target ID: CHEMBL2362994 |
0.1 µM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | HEPSERA Approved UseHEPSERA is indicated for the treatment of chronic hepatitis B in patients 12 years of age and older with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease. This indication is based on histological, virological, biochemical, and serological responses in adult patients with HBeAg+ and HBeAg- chronic hepatitis B with compensated liver function, and with clinical evidence of lamivudine-resistant hepatitis B virus with either compensated or decompensated liver function. For patients 12 to <18 years of age, the indication is based on virological and biochemical responses in patients with HBeAg+ chronic hepatitis B virus infection with compensated liver function. HEPSERA is a nucleotide analogue indicated for the treatment of chronic hepatitis B in patients ≥12 years of age. (1) Launch Date1.03248003E12 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
18.4 ng/mL |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ADEFOVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
220 ng × h/mL |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ADEFOVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.48 h |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ADEFOVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
96% |
10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered: |
ADEFOVIR plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: |
unhealthy, 12 - 17 years n = 15 Health Status: unhealthy Condition: chronic hepatitis B Age Group: 12 - 17 years Sex: M+F Population Size: 15 Sources: |
Other AEs: Rhinorrhea, Sneezing... Other AEs: Rhinorrhea (1 patient) Sources: Sneezing (1 patient) Blister (1 patient) |
0.3 mg/kg 1 times / day multiple, oral Recommended Dose: 0.3 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.3 mg/kg, 1 times / day Sources: |
unhealthy, 2 - 6 years n = 13 Health Status: unhealthy Condition: chronic hepatitis B Age Group: 2 - 6 years Sex: M+F Population Size: 13 Sources: |
|
0.3 mg/kg 1 times / day multiple, oral Recommended Dose: 0.3 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.3 mg/kg, 1 times / day Sources: |
unhealthy, 7 - 11 years n = 19 Health Status: unhealthy Condition: chronic hepatitis B Age Group: 7 - 11 years Sex: M+F Population Size: 19 Sources: |
Other AEs: Headache, Vertigo... Other AEs: Headache (1 patient) Sources: Vertigo (1 patient) Disturbance in attention (1 patient) Disorder eye (1 patient) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Blister | 1 patient | 10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: |
unhealthy, 12 - 17 years n = 15 Health Status: unhealthy Condition: chronic hepatitis B Age Group: 12 - 17 years Sex: M+F Population Size: 15 Sources: |
Rhinorrhea | 1 patient | 10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: |
unhealthy, 12 - 17 years n = 15 Health Status: unhealthy Condition: chronic hepatitis B Age Group: 12 - 17 years Sex: M+F Population Size: 15 Sources: |
Sneezing | 1 patient | 10 mg 1 times / day multiple, oral Recommended Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: |
unhealthy, 12 - 17 years n = 15 Health Status: unhealthy Condition: chronic hepatitis B Age Group: 12 - 17 years Sex: M+F Population Size: 15 Sources: |
Disorder eye | 1 patient | 0.3 mg/kg 1 times / day multiple, oral Recommended Dose: 0.3 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.3 mg/kg, 1 times / day Sources: |
unhealthy, 7 - 11 years n = 19 Health Status: unhealthy Condition: chronic hepatitis B Age Group: 7 - 11 years Sex: M+F Population Size: 19 Sources: |
Disturbance in attention | 1 patient | 0.3 mg/kg 1 times / day multiple, oral Recommended Dose: 0.3 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.3 mg/kg, 1 times / day Sources: |
unhealthy, 7 - 11 years n = 19 Health Status: unhealthy Condition: chronic hepatitis B Age Group: 7 - 11 years Sex: M+F Population Size: 19 Sources: |
Headache | 1 patient | 0.3 mg/kg 1 times / day multiple, oral Recommended Dose: 0.3 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.3 mg/kg, 1 times / day Sources: |
unhealthy, 7 - 11 years n = 19 Health Status: unhealthy Condition: chronic hepatitis B Age Group: 7 - 11 years Sex: M+F Population Size: 19 Sources: |
Vertigo | 1 patient | 0.3 mg/kg 1 times / day multiple, oral Recommended Dose: 0.3 mg/kg, 1 times / day Route: oral Route: multiple Dose: 0.3 mg/kg, 1 times / day Sources: |
unhealthy, 7 - 11 years n = 19 Health Status: unhealthy Condition: chronic hepatitis B Age Group: 7 - 11 years Sex: M+F Population Size: 19 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 6, 16 |
inconclusive | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P2.pdf Page: 26.0 |
inconclusive | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0 |
no |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P2.pdf Page: 26.0 |
inconclusive | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0 |
no | |||
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0 |
no | |||
no | ||||
yes | ||||
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonylmethoxyethyl)adenine, a potent anti-human immunodeficiency virus compound. | 1991 Feb 15 |
|
Susceptibility of lamivudine-resistant hepatitis B virus to other reverse transcriptase inhibitors. | 1999 Jun |
|
In vitro selection of mutations in the human immunodeficiency virus type 1 reverse transcriptase that decrease susceptibility to (-)-beta-D-dioxolane-guanosine and suppress resistance to 3'-azido-3'-deoxythymidine. | 2000 Jul |
|
In vivo anti-papillomavirus activity of nucleoside analogues including cidofovir on CRPV-induced rabbit papillomas. | 2000 Nov |
|
A new acyclic heterodinucleotide active against human immunodeficiency virus and herpes simplex virus. | 2000 Sep |
|
Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA. | 2001 Apr 23 |
|
Acute liver graft failure due to emergence of lamivudine resistant hepatitis B virus: rapid resolution during treatment with adefovir. | 2001 Dec |
|
Intramolecular stacking interactions in ternary copper(II) complexes formed with 2,2'-bipyridine or 1,10-phenanthroline and 9-(4-phosphonobutyl)adenine (dPMEA), the carba relative of the antiviral nucleotide analogue 9. | 2001 Mar |
|
6-[2-(Phosphonomethoxy)alkoxy]pyrimidines with antiviral activity. | 2002 Apr 25 |
|
Novel nucleoside analogue MCC-478 (LY582563) is effective against wild-type or lamivudine-resistant hepatitis B virus. | 2002 Aug |
|
Intramolecular stacking interactions in ternary copper(II) complexes formed by a heteroaromatic amine and 9-[2-(2-phosphonoethoxy)ethyl]adenine, a relative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine. | 2004 Dec |
|
Quantification of isomeric equilibria formed by metal ion complexes of 8-[2-(phosphonomethoxy)ethyl]-8-azaadenine (8,8aPMEA) and 9-[2-(phosphonomethoxy)ethyl]-8-azaadenine (9,8aPMEA). Derivatives of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). | 2004 Dec |
|
Metal ion complexes of antivirally active nucleotide analogues. Conclusions regarding their biological action. | 2004 Mar 30 |
|
Antiviral potential of a new generation of acyclic nucleoside phosphonates, the 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines. | 2005 |
|
Cross-resistance testing of next-generation nucleoside and nucleotide analogues against lamivudine-resistant HBV. | 2005 |
|
Acid-base and metal-ion-binding properties of 9-[2-(2-phosphonoethoxy)ethyl]adenine (PEEA), a relative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA). An exercise on the quantification of isomeric complex equilibria in solution. | 2005 Jul 11 |
|
Inhibition of human liver microsomal cytochrome P450 activities by adefovir and tenofovir. | 2006 Dec |
|
In vivo effects of antiviral acyclic nucleoside phosphonate 9-[2-(phosphonomethoxy)ethyl]adenine (adefovir) on cytochrome P450 system of rat liver microsomes. | 2006 May |
|
Improved outcome of chronic hepatitis B after heart transplantation by long-term antiviral therapy. | 2006 Nov |
|
Synthesis and antiviral evaluation of alkoxyalkyl esters of acyclic purine and pyrimidine nucleoside phosphonates against HIV-1 in vitro. | 2006 Oct |
|
Decompensated lamivudine-resistant hepatitis B virus-related cirrhosis treated successfully with adefovir dipivoxil allowing surgery for hepatocellular carcinoma. | 2007 |
|
Substrate overlap between Mrp4 and Abcg2/Bcrp affects purine analogue drug cytotoxicity and tissue distribution. | 2007 Jul 15 |
|
Prophylaxsis against recurrance of hepatitis B virus after liver transplantation: a retrospective analysis spanning 20 years. | 2008 Jan |
|
Renal side effects of adefovir in hepatitis B virus-(HBV) positive kidney allograft recipients. | 2009 Jan |
Patents
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Classification Tree | Code System | Code | ||
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NDF-RT |
N0000175459
Created by
admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
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NDF-RT |
N0000175459
Created by
admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
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NCI_THESAURUS |
C97452
Created by
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LIVERTOX |
NBK548633
Created by
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NDF-RT |
N0000175656
Created by
admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
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NDF-RT |
N0000009947
Created by
admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
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NDF-RT |
N0000175459
Created by
admin on Sat Dec 16 17:53:19 UTC 2023 , Edited by admin on Sat Dec 16 17:53:19 UTC 2023
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134512
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7313
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CHEMBL484
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C61526
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m1409
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6GQP90I798
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6GQP90I798
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DTXSID6046214
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106941-25-7
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16521
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C053001
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Adefovir
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100000090470
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GG-19
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60172
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SUB05264MIG
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Adefovir
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DB13868
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8079
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2469
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ACTIVE MOIETY
PRODRUG (METABOLITE ACTIVE)
PRODRUG (METABOLITE ACTIVE)