PRADEFOVIR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H19ClN5O4P
Molecular Weight	423.791
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=C2N=CN(CCOC[P@@]3(=O)OCC[C@H](O3)C4=CC(Cl)=CC=C4)C2=NC=N1

InChI

InChIKey=GWNHAOBXDGOXRR-HJFSHJIFSA-N

InChI=1S/C17H19ClN5O4P/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/h1-3,8-10,14H,4-7,11H2,(H2,19,20,21)/t14-,28+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C17H19ClN5O4P
Molecular Weight	423.791
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021449s020lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Multidrug resistance-associated protein 4 14 Target ID: CHEMBL1743128 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23956101	Inhibitor 8504	133.0 µM [IC50]
Bile salt export pump 15 Target ID: CHEMBL6020 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23956101	Inhibitor 8504	46.0 µM [IC50]
Canalicular multispecific organic anion transporter 1 21 Target ID: CHEMBL5748 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23956101	Inhibitor 8504	133.0 µM [IC50]
Canalicular multispecific organic anion transporter 2 8 Target ID: CHEMBL5918 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23956101	Inhibitor 8504	133.0 µM [IC50]
DNA polymerase/reverse transcriptase 10 Target ID: CHEMBL2362994 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021449s020lbl.pdf	Inhibitor 8504	0.1 µM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic hepatitis B 16 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021449s020lbl.pdf	Primary		Approved 8583	HEPSERA Approved Use HEPSERA 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 Date 2002

C_max

Value	Dose	Co-administered	Analyte	Population
18.4 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021449s009lbl.pdf	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 DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021449s009lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.48 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021449s009lbl.pdf	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
96% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021449s009lbl.pdf	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: https://pubmed.ncbi.nlm.nih.gov/18276803/	unhealthy, 12 - 17 years Health Status: unhealthy Age Group: 12 - 17 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/	Other AEs: Rhinorrhea, Sneezing... Other AEs: Rhinorrhea (1 patient) Sneezing (1 patient) Blister (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/
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: https://pubmed.ncbi.nlm.nih.gov/18276803/	unhealthy, 2 - 6 years Health Status: unhealthy Age Group: 2 - 6 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/	Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/
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: https://pubmed.ncbi.nlm.nih.gov/18276803/	unhealthy, 7 - 11 years Health Status: unhealthy Age Group: 7 - 11 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/	Other AEs: Headache, Vertigo... Other AEs: Headache (1 patient) Vertigo (1 patient) Disturbance in attention (1 patient) Disorder eye (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/

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: https://pubmed.ncbi.nlm.nih.gov/18276803/	unhealthy, 12 - 17 years Health Status: unhealthy Age Group: 12 - 17 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/
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: https://pubmed.ncbi.nlm.nih.gov/18276803/	unhealthy, 12 - 17 years Health Status: unhealthy Age Group: 12 - 17 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/
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: https://pubmed.ncbi.nlm.nih.gov/18276803/	unhealthy, 12 - 17 years Health Status: unhealthy Age Group: 12 - 17 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/
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: https://pubmed.ncbi.nlm.nih.gov/18276803/	unhealthy, 7 - 11 years Health Status: unhealthy Age Group: 7 - 11 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/
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: https://pubmed.ncbi.nlm.nih.gov/18276803/	unhealthy, 7 - 11 years Health Status: unhealthy Age Group: 7 - 11 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/
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: https://pubmed.ncbi.nlm.nih.gov/18276803/	unhealthy, 7 - 11 years Health Status: unhealthy Age Group: 7 - 11 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/
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: https://pubmed.ncbi.nlm.nih.gov/18276803/	unhealthy, 7 - 11 years Health Status: unhealthy Age Group: 7 - 11 years Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/18276803/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 substrate 1946	inhibitor 2438 substrate 1193	inhibitor 2507 substrate 1388

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP2C19 2057 P-gp 1741	OAT1 395 OCT2 434 MRP4 91 CYP1A2 1197 CYP2C19 1119 P-gp 2052	CYP 74

Drug as perpetrator

Target	Modality	Activity
CYP 150	inducer 1966 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 6, 16	inconclusive
P-gp 1932	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P2.pdf Page: 26.0	inconclusive
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0	no
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0	no
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0	no
CYP3A4 2633	inhibitor 4027 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
P-gp 2052	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P2.pdf Page: 26.0	inconclusive
CYP1A2 1197	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0	no
CYP2C19 1119	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0	no
CYP2C9 1193	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0	no
CYP2D6 1388	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0	no
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-449_Hepsera_biopharmr_P1.pdf Page: 15.0	no
OCT2 434	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16454695/	no
MRP4 91	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16454695/	yes
OAT1 395	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/16454695/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:2469	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:2469
ChemicalBook	CB2698137	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2698137
eMolecules	901335	https://www.emolecules.com/cgi-bin/more?vid=901335
ZINC	ZINC000021297308	http://zinc15.docking.org/substances/ZINC000021297308

PubMed

Title	Date	PubMed
Gene induction for the treatment of methylmalonic aciduria.	2009-04	19199343
Association of lamivudine-resistant mutational patterns with the antiviral effect of adefovir in patients with chronic hepatitis B.	2009-03	19152409
Telbivudine, a nucleoside analog inhibitor of HBV polymerase, has a different in vitro cross-resistance profile than the nucleotide analog inhibitors adefovir and tenofovir.	2009-02	19028525
Renal side effects of adefovir in hepatitis B virus-(HBV) positive kidney allograft recipients.	2009-01	19203548
Permeation enhancer dodecyl 6-(dimethylamino)hexanoate increases transdermal and topical delivery of adefovir: influence of pH, ion-pairing and skin species.	2008-11	18675907
Living donor liver transplantation for hepatitis B associated liver diseases: a 10-year experience in a single center.	2008-09-18	18795708
Side-effects of cidofovir in the treatment of recurrent respiratory papillomatosis.	2008-08	18458927
The human multidrug resistance protein 4 (MRP4, ABCC4): functional analysis of a highly polymorphic gene.	2008-06	18364470
Short-term overlap lamivudine treatment with adefovir dipivoxil in patients with lamivudine-resistant chronic hepatitis B.	2008-03-21	18350610
[Factors affecting initial virologic response and emergence of resistant mutants after adefovir treatment in lamivudine-resistant chronic hepatitis B patients].	2008-03	18367858
Prophylaxsis against recurrance of hepatitis B virus after liver transplantation: a retrospective analysis spanning 20 years.	2008-01	17983429
Successful treatment of an entecavir-resistant hepatitis B virus variant.	2007-12	17935165
Secretion of antiretroviral chemokines by human cells cultured with acyclic nucleoside phosphonates.	2007-11-21	17716649
Some new acyclic nucleotide analogues as antiviral prodrugs: synthesis and bioactivities in vitro.	2007-11-15	17888662
Redetection of HBV lamivudine-resistant mutations in a patient under entecavir therapy, who had been treated sequentially with nucleos(t)ide analogues.	2007-11	17854030
In vitro drug susceptibility analysis of hepatitis B virus clinical quasispecies populations.	2007-10	17687019
Combination therapy in liver transplant recipients with hepatitis B virus without hepatitis B immune globulin.	2007-10	17404847
Substrate overlap between Mrp4 and Abcg2/Bcrp affects purine analogue drug cytotoxicity and tissue distribution.	2007-07-15	17638908
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.	2007-04-06	17417971
Design and synthesis of novel bis(L-amino acid) ester prodrugs of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) with improved anti-HBV activity.	2007-01-15	17074481
Pronounced in vitro and in vivo antiretroviral activity of 5-substituted 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy] pyrimidines.	2007-01	17124193
Decompensated lamivudine-resistant hepatitis B virus-related cirrhosis treated successfully with adefovir dipivoxil allowing surgery for hepatocellular carcinoma.	2007	17409599
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.	2006-12-28	17181162
Inhibition of human liver microsomal cytochrome P450 activities by adefovir and tenofovir.	2006-12	17162464
The flounder organic anion transporter fOat has sequence, function, and substrate specificity similarity to both mammalian Oat1 and Oat3.	2006-12	16857889
Improved outcome of chronic hepatitis B after heart transplantation by long-term antiviral therapy.	2006-11	17052272
Synthesis and antiviral evaluation of alkoxyalkyl esters of acyclic purine and pyrimidine nucleoside phosphonates against HIV-1 in vitro.	2006-10	16630664
Favorable outcome of liver transplantation despite a high hepatitis B virus replication: beyond the limits?	2006-09	16913979
In vivo effects of antiviral acyclic nucleoside phosphonate 9-[2-(phosphonomethoxy)ethyl]adenine (adefovir) on cytochrome P450 system of rat liver microsomes.	2006-05	16416053
In vitro comparison of antiviral drugs against feline herpesvirus 1.	2006-04-26	16640781
Cellular and virological mechanisms of HBV drug resistance.	2006-02	16364492
Virologic response and resistance to adefovir in patients with chronic hepatitis B.	2006-02	16338024
Purine P1 receptor-dependent immunostimulatory effects of antiviral acyclic analogues of adenine and 2,6-diaminopurine.	2006-01-13	16371225
Introduction to chronic hepatitis B infection.	2006	16448446
cycloSal-PMEA and cycloAmb-PMEA: potentially new phosphonate prodrugs based on the cycloSal-pronucleotide approach.	2005-12-15	16335932
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.	2005-07-11	15998039
Spectrum of antiviral activity of o-(acetoxyphenyl)hept-2-ynyl sulphide (APHS).	2005-05	15848298
Deoxythreosyl phosphonate nucleosides as selective anti-HIV agents.	2005-04-13	15810840
Novel acyclic nucleoside phosphonate analogues with potent anti-hepatitis B virus activities.	2005-03	15728921
In vitro activity of structurally diverse nucleoside analogs against human immunodeficiency virus type 1 with the K65R mutation in reverse transcriptase.	2005-03	15728915
Susceptibilities of several clinical varicella-zoster virus (VZV) isolates and drug-resistant VZV strains to bicyclic furano pyrimidine nucleosides.	2005-03	15728906
Antiviral potential of a new generation of acyclic nucleoside phosphonates, the 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines.	2005	16247948
Cross-resistance testing of next-generation nucleoside and nucleotide analogues against lamivudine-resistant HBV.	2005	16152756
6-[2-phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines: a new class of acyclic pyrimidine nucleoside phosphonates with antiviral activity.	2004-10	15571252
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	18365084
Chemotherapy of feline immunodeficiency virus infection.	1991-11-15	1666108
Early therapy of feline leukemia virus infection (FeLV-FAIDS) with 9-(2-phosphonylmethoxyethyl)adenine (PMEA).	1991-07	1663730
9-[(2RS)-3-fluoro-2-phosphonylmethoxypropyl] derivatives of purines: a class of highly selective antiretroviral agents in vitro and in vivo.	1991-06-01	1711214
Intracellular metabolism and mechanism of anti-retrovirus action of 9-(2-phosphonylmethoxyethyl)adenine, a potent anti-human immunodeficiency virus compound.	1991-02-15	1705039
Herpes simplex virus-specified DNA polymerase is the target for the antiviral action of 9-(2-phosphonylmethoxyethyl)adenine.	1991-01-05	1845964

Patents

Sample Use Guides

In Vivo Use Guide

One tablet containing 10 mg adefovir dipivoxil once daily orally

Route of Administration: Oral

In Vitro Use Guide

The concentration of adefovir that inhibited 50% of viral DNA synthesis (EC50) in HBV transfected human hepatoma cell lines ranged from 0.2 to 2.5 uM.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:18:04 GMT 2025` Edited by `admin` on `Mon Mar 31 18:18:04 GMT 2025`
Record UNII	GZE85Q9Q61
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

Pradefovir [WHO-DD]

Preferred Name

English

PRADEFOVIR

Official Name

English

pradefovir [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C281