Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C17H19ClN5O4P.CH4O3S |
Molecular Weight | 519.896 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 2 / 2 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CS(O)(=O)=O.NC1=C2N=CN(CCOC[P@@]3(=O)OCC[C@H](O3)C4=CC=CC(Cl)=C4)C2=NC=N1
InChI
InChIKey=JXQUAHHUSMJUFV-HZPZRMRQSA-N
InChI=1S/C17H19ClN5O4P.CH4O3S/c18-13-3-1-2-12(8-13)14-4-6-26-28(24,27-14)11-25-7-5-23-10-22-15-16(19)20-9-21-17(15)23;1-5(2,3)4/h1-3,8-10,14H,4-7,11H2,(H2,19,20,21);1H3,(H,2,3,4)/t14-,28+;/m0./s1
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 Date2002 |
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 |
---|---|---|
9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] derivatives of purines: a class of highly selective antiretroviral agents in vitro and in vivo. | 1991 Jun 1 |
|
Synthesis and in vitro evaluation of a phosphonate prodrug: bis(pivaloyloxymethyl) 9-(2-phosphonylmethoxyethyl)adenine. | 1992 Sep |
|
Effect of acyclic nucleoside phosphonates on the HIV-1 integrase in vitro. | 1999 Apr-May |
|
Hydroxyurea potentiates the antiherpesvirus activities of purine and pyrimidine nucleoside and nucleoside phosphonate analogs. | 1999 Dec |
|
Sensitivity of L-(-)2,3-dideoxythiacytidine resistant hepatitis B virus to other antiviral nucleoside analogues. | 1999 Jun 15 |
|
Prevalence and characteristics of multinucleoside-resistant human immunodeficiency virus type 1 among European patients receiving combinations of nucleoside analogues. | 2000 Aug |
|
Lamivudine, adefovir and tenofovir exhibit long-lasting anti-hepatitis B virus activity in cell culture. | 2000 Jan |
|
Drug resistance and drug combination features of the human immunodeficiency virus inhibitor, BCH-10652 [(+/-)-2'-deoxy-3'-oxa-4'-thiocytidine, dOTC]. | 2000 Jul |
|
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 |
|
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 |
|
Cross-resistance testing of antihepadnaviral compounds using novel recombinant baculoviruses which encode drug-resistant strains of hepatitis B virus. | 2001 Jun |
|
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 |
|
In vitro susceptibilities of wild-type or drug-resistant hepatitis B virus to (-)-beta-D-2,6-diaminopurine dioxolane and 2'-fluoro-5-methyl-beta-L-arabinofuranosyluracil. | 2001 Sep |
|
Fanconi syndrome and renal failure induced by tenofovir: a first case report. | 2002 Dec |
|
Antivaccinia activities of acyclic nucleoside phosphonate derivatives in epithelial cells and organotypic cultures. | 2002 Nov |
|
In vitro activity of potential anti-poxvirus agents. | 2003 Jan |
|
Intrinsic acid-base properties of purine derivatives in aqueous solution and comparison of the acidifying effects of platinum(II) coordinated to N1 or N7: acidifying effects are reciprocal and the proton "outruns" divalent metal ions. | 2003 Jan 13 |
|
Evaluation of nucleoside phosphonates and their analogs and prodrugs for inhibition of orthopoxvirus replication. | 2003 Jul |
|
Nickel(II), copper(II) and zinc(II) complexes of 9-[2- (phosphonomethoxy)ethyl]-8-azaadenine (9,8aPMEA), the 8-aza derivative of the antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl] adenine (PMEA). Quantification of four isomeric species in aqueous solution. | 2004 |
|
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 |
|
Synthesis and antiviral activity of 2,4-diamino-5-cyano-6-[2-(phosphonomethoxy)ethoxy]pyrimidine and related compounds. | 2004 Jun 15 |
|
In vitro selection of drug-resistant varicella-zoster virus (VZV) mutants (OKA strain): differences between acyclovir and penciclovir? | 2004 Mar |
|
Metal ion complexes of antivirally active nucleotide analogues. Conclusions regarding their biological action. | 2004 Mar 30 |
|
6-[2-phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines: a new class of acyclic pyrimidine nucleoside phosphonates with antiviral activity. | 2004 Oct |
|
Combinations of adefovir with nucleoside analogs produce additive antiviral effects against hepatitis B virus in vitro. | 2004 Oct |
|
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 |
|
Synthesis, in vitro antiviral evaluation, and stability studies of novel alpha-borano-nucleotide analogues of 9-[2-(phosphonomethoxy)ethyl]adenine and (R)-9-[2-(phosphonomethoxy)propyl]adenine. | 2006 Dec 28 |
|
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 |
|
Sequential emergence and clinical implications of viral mutants with K70E and K65R mutation in reverse transcriptase during prolonged tenofovir monotherapy in rhesus macaques with chronic RT-SHIV infection. | 2007 Apr 6 |
|
Pronounced in vitro and in vivo antiretroviral activity of 5-substituted 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy] pyrimidines. | 2007 Jan |
|
Design and synthesis of novel bis(L-amino acid) ester prodrugs of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) with improved anti-HBV activity. | 2007 Jan 15 |
|
Substrate overlap between Mrp4 and Abcg2/Bcrp affects purine analogue drug cytotoxicity and tissue distribution. | 2007 Jul 15 |
|
Secretion of antiretroviral chemokines by human cells cultured with acyclic nucleoside phosphonates. | 2007 Nov 21 |
|
In vitro drug susceptibility analysis of hepatitis B virus clinical quasispecies populations. | 2007 Oct |
|
Combination therapy in liver transplant recipients with hepatitis B virus without hepatitis B immune globulin. | 2007 Oct |
|
Gene induction for the treatment of methylmalonic aciduria. | 2009 Apr |
|
Renal side effects of adefovir in hepatitis B virus-(HBV) positive kidney allograft recipients. | 2009 Jan |
Patents
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Official Name | English | ||
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Common Name | English | ||
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Common Name | English | ||
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Common Name | English |
Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C1557
Created by
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NCI_THESAURUS |
C281
Created by
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0D5204ZSIX
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300000044516
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QQ-64
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9604653
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DB05478
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DTXSID00211558
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625095-61-6
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C66454
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C497721
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CHEMBL2111102
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ACTIVE MOIETY
SUBSTANCE RECORD