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Showing drug card for Adefovir Dipivoxil (DB00718)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:45
Primary Accession Number DB00718
Secondary Accession Number
  • APRD00781
Name Adefovir Dipivoxil
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Adefovir dipivoxil, previously called bis-POM PMEA, with trade names Preveon and Hepsera, is an orally-administered nucleotide analog reverse transcriptase inhibitor (ntRTI) used for treatment of hepatitis B. It is a failed treatment for HIV. [Wikipedia]
Synonyms
  1. ADV
  2. Adefovir
  3. Adefovir pivoxil
  4. Adefovirdipivoxl
  5. GS-840
  6. PMEA
  7. adefovir dipivoxil
  8. bis-POM PMEA
Brand Names
  1. Hepsera
  2. Preveon
Brand Mixtures Not Available
Chemical IUPAC Name [2-(6-aminopurin-9-yl)ethoxymethyl-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate
Chemical Formula C20H32N5O8P
Chemical Structure Structure
CAS Registry Number 142340-99-6
InChI Identifier InChI=1/C20H32N5O8P/c1-19(2,3)17(26)30-11-32-34(28,33-12-31-18(27)20(4,5)6)13-29-8-7-25-10-24-14-15(21)22-9-23-16(14)25/h9-10H,7-8,11-13H2,1-6H3,(H2,21,22,23)/f/h21H2
InChI Key WOZSCQDILHKSGG-QVUQFMIFCQ
KEGG Drug D01655 Link Image
KEGG Compound Not Available
PubChem Compound 60871 Link Image
PubChem Substance 7848718 Link Image
ChEBI ID Not Available
PharmGKB ID Not Available
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link http://www.rxlist.com/cgi/generic3/hepsera.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Adefovir Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 501.4705
Monoisotopic Molecular Weight 501.1988
State Solid
Melting Point Not Available
Experimental Water Solubility 19 mg/mL at pH 2.0 and 0.4 mg/mL at pH 7.2. Source: PhysProp
Predicted Water Solubility 6.33e-01 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 0.8 Source: PhysProp
Predicted LogP 1.50 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.90 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CC(C)(C)C(=O)OCOP(=O)(COCCN1C=NC2=C(N)N=CN=C12)OCOC(=O)C(C)(C)C
Canonical SMILES CC(C)(C)C(=O)OCOP(=O)(COCCN1C=NC2=C(N)N=CN=C12)OCOC(=O)C(C)(C)C
Drug Category
  • Antiviral Agents
  • Reverse Transcriptase Inhibitors
ATC Codes
AHFS Codes
  • 08:18.32
Indication For the treatment of chronic hepatitis B in adults with evidence of active viral replication and either evidence of persistent elevations in serum aminotransferases (ALT or AST) or histologically active disease.
Pharmacology Adefovir dipivoxil a diester prodrug of adefovir. Adefovir is an acyclic nucleotide analog with activity against human hepatitis B virus (HBV). The concentration of adefovir that inhibited 50% of viral DNA synthesis (IC50) in vitro ranged from 0.2 to 2.5 μM in HBV transfected human hepatoma cell lines. The combination of adefovir with lamivudine showed additive anti-HBV activity.
Mechanism of Action Adefovir dipivoxil is a prodrug of adefovir. 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. The inhibition constant (Ki) for adefovir diphosphate for HBV DNA polymerase was 0.1 μM. Adefovir diphosphate is a weak inhibitor of human DNA polymerases α and γ with Ki values of 1.18 μM and 0.97μM, respectively.
Absorption Approximate oral bioavailability is 59%.
Toxicity Renal tubular nephropathy characterized by histological alterations and/or increases in BUN and serum creatinine was the primary dose-limiting toxicity associated with administration of adefovir dipivoxil in animals. Nephrotoxicity was observed in animals at systemic exposures approximately 3–10 times higher than those in humans at the recommended therapeutic dose of 10 mg/day.
Protein Binding ≤4% over the adefovir concentration range of 0.1 to 25 μg/mL
Biotransformation Following oral administration, adefovir dipivoxil is rapidly converted to adefovir. Forty-five percent of the dose is recovered as adefovir in the urine over 24 hours at steady state following 10 mg oral doses. Adefovir is not a substrate of the cytochrome P450 enzymes.
Half Life Terminal elimination half-life of 7.48 ± 1.65 hours
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions Not Available
Food Interactions
  • Take without regard to meals.
Pathways Not Available
General References
  1. Wikipedia Link Image
  2. RxList Link Image
Organisms Affected
  • Hepatitis B virus
Targets
  1. P protein [Includes: DNA-directed DNA polymerase
Drug Target 1 [top]
Target 1 ID 342
Target 1 Name P protein [Includes: DNA-directed DNA polymerase
Target 1 Synonyms Not Available
Target 1 Gene Name P
Target 1 Protein Sequence >P protein [Includes: DNA-directed DNA polymerase 
MPLSYQHFRRLLLLDDEAGPLEEELPRLADEGLNRHVAEELNLGNLNVSIPWTHKVGNFT
GLYSSTVPVFNPHWKTPSFPNIHLHQDIIKKCEQFVGPLTVNEKRRLQLIMPARFYPKVT
KYLPLDKGIKPYYPEHLVNHYFQTRHYLHTLWKAGVLYKRETTHSASFCGSPYSWEQELQ
HGAESFHQQSSGILSRPPVGSSLQSKHCKSRLGLQSQQGLLARRQQGRSWSIRAGIHPTA
RRPFGVEPSGSGHTTNLASKSASCLHQSPVRKATYPSVSTFEKHSSSGHAVELHNLPPNS
ARSQSERPVSPCWWLQFRNSKPCSDYCLSHIVNLLEDWGPCAEHGEHHIRIPRTPARVTG
GVFLVDKNPHNTEESRLVVDFSQFSRGNHRVSWPKFAVPNLQSLTNLLSSNLSWLSLDVS
AAFYHLPLHPAAMPHLLVGSSGLSRYVARLSSDSRIFNHQHGTMQNLHDSCSRNLYVSLL
LLYQTFGRKLHLYSHPIILGFRKIPMGVGLSPFLLAQFTSAICSVVRRAFPHCLAFSYMD
DVVLGAKTVHHLESLFTAVTNFLLSLGIHLNPNKTKRWGYSLHFMGYVIGCYGSLPQDHI
IQKIKECFRKLPVNRPIDWKVCQRIVGLLGFAAPFTQCGYPALMPLYACIQSKQAFTFSP
TYKAFLCKQYLNLYPVARQRPGLCQVFADATPTGWGLVMGHQRMRGTFQAPLPIHTAELL
AACFARSRSGANILGTDNSVVLSRKYTSFPWLLGCAANWILRGTSFVYVPSALNPADDPS
RGRLGLSRPLLRLPFRPTTGRTSLYADSPSVPSHLPDRVHFASPLHVAWRPP
Target 1 Number of Residues 845
Target 1 Molecular Weight 93591
Target 1 Theoretical pI 10.05
Target 1 GO Classification
Function
RNA-directed DNA polymerase activity
RNA binding
transferase activity
transferase activity, transferring phosphorus-containing groups
nucleotidyltransferase activity
DNA-directed DNA polymerase activity
binding
nucleic acid binding
DNA binding
catalytic activity
hydrolase activity
hydrolase activity, acting on ester bonds
nuclease activity
endonuclease activity
endoribonuclease activity
endoribonuclease activity, producing 5'-phosphomonoesters
ribonuclease H activity
Process
RNA-dependent DNA replication
physiological process
metabolism
cellular metabolism
nucleobase, nucleoside, nucleotide and nucleic acid metabolism
DNA metabolism
DNA replication
Component
Not Available
Target 1 General Function Involved in RNA binding
Target 1 Specific Function Not Available
Target 1 Pathways
Name SMPDB Link KEGG Link
DNA polymerase map03030 Link Image
Purine metabolism SMP00050 Link Image map00230 Link Image
Pyrimidine metabolism SMP00046 Link Image map00240 Link Image
Target 1 Reactions
  • deoxynucleoside triphosphate + DNAn = diphosphate + DNAn+1
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • None
Target 1 Essentiality Essential
Target 1 GenBank ID Protein 329670 Link Image
Target 1 UniProtKB/Swiss-Prot ID P24024 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name DPOL_HBVIA Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Cytoplasmic
Target 1 Gene Sequence >2499 bp 
ATGCCCCTATCTTATCAACACTTCCGGAGACTACTGTTGTTAGACGACGAGGCAGGTCCC
CTAGAAGAAGAACTCCCTCGCCTCGCAGACGAAGGTCTCAATCGCCACGTCGCAGAAGAA
CTCAATCTCGGGAATCTCAATGTTAGTATTCCCTGGACTCATAAGGTGGGAAACTTTACG
GGGCTTTATTCTTCTACTGTTCCTGTCTTTAACCCTCATTGGAAAACACCCTCTTTTCCT
AATATACATTTACACCAAGACATTATCAAAAAATGTGAACAATTTGTAGGCCCACTCACA
GTCAATGAGAAAAGAAGACTGCAATTGATTATGCCTGCTAGGTTTTATCCAAAGGTTACC
AAATATTTGCCATTGGATAAGGGTATTAAACCTTATTATCCAGAACATCTAGTTAATCAT
TACTTCCAAACCAGACATTATTTACACACTCTATGGAAGGCGGGTGTATTATATAAGAGA
GAAACTACACATAGCGCCTCATTTTGTGGGTCACCATATTCCTGGGAACAAGAGCTACAG
CATGGGGCAGAATCTTTCCACCAGCAATCCTCTGGGATTCTTTCCCGACCACCAGTTGGA
TCCAGCCTTCAGAGCAAACACTGCAAATCCAGATTGGGACTTCAATCCCAACAAGGACTC
CTGGCCAGACGCCAACAAGGTAGGAGCTGGAGCATTCGGGCTGGGATTCACCCCACCGCA
CGGAGGCCTTTTGGGGTGGAGCCCTCAGGCTCAGGGCATACTACAAACCTTGCCAGCAAA
TCCGCCTCCTGCCTCCACCAATCGCCAGTCAGGAAGGCAACCTACCCCTCTGTCTCCACC
TTTGAGAAACACTCATCCTCAGGCCATGCAGTGGAACTCCACAACCTTCCACCAAACTCT
GCAAGATCCCAGAGTGAGAGGCCTGTATCTCCCTGCTGGTGGCTCCAGTTCAGGAACAGT
AAACCCTGTTCCGACTACTGTCTCTCCCATATCGTCAATCTTCTCGAGGATTGGGGACCC
TGCGCTGAACATGGAGAACATCACATCAGGATTCCTAGGACCCCTGCTCGTGTTACAGGC
GGGGTTTTTCTTGTTGACAAAAATCCTCACAATACCGAAGAGTCTAGACTCGTGGTGGAC
TTCTCTCAATTTTCTAGGGGGAACCACCGTGTGTCTTGGCCAAAATTCGCAGTCCCCAAC
CTCCAATCACTCACCAACCTCCTGTCCTCCAACTTGTCCTGGTTATCGCTGGATGTGTCT
GCGGCGTTTTATCATCTTCCTCTTCATCCTGCTGCTATGCCTCATCTTCTTGTTGGTTCT
TCTGGACTATCAAGGTATGTTGCCCGTTTGTCCTCTGATTCCAGGATCTTCAACCACCAG
CACGGGACCATGCAGAACCTGCACGACTCCTGCTCAAGGAACCTCTATGTATCCCTCCTG
TTGCTGTACCAAACCTTCGGACGGAAATTGCACCTGTATTCCCATCCCATCATCCTGGGC
TTTCGGAAAATTCCTATGGGAGTGGGCCTCAGCCCGTTTCTCCTGGCTCAGTTTACTAGT
GCCATTTGTTCAGTGGTTCGTAGGGCTTTCCCCCACTGTTTGGCTTTTAGTTATATGGAT
GATGTGGTATTGGGGGCCAAAACTGTTCACCATCTTGAGTCCCTTTTTACCGCTGTTACC
AATTTTCTTTTGTCTTTGGGTATACATCTAAACCCTAACAAAACAAAAAGATGGGGTTAC
TCTTTACATTTTATGGGCTATGTCATTGGATGTTATGGGTCTTTGCCACAAGATCACATC
ATACAGAAAATCAAAGAATGTTTTAGAAAACTTCCTGTTAACAGGCCTATTGATTGGAAA
GTCTGTCAACGTATTGTGGGTCTTTTGGGATTTGCTGCTCCTTTTACACAATGTGGTTAT
CCTGCTTTAATGCCCTTGTATGCATGTATTCAATCTAAGCAGGCTTTCACTTTCTCGCCA
ACTTACAAGGCCTTTCTGTGTAAACAATACCTGAACCTTTACCCCGTTGCCCGGCAACGC
CCAGGTCTGTGCCAAGTGTTTGCTGACGCAACCCCCACTGGCTGGGGCTTGGTCATGGGC
CATCAGCGCATGCGTGGAACCTTTCAGGCTCCTCTGCCGATCCATACTGCGGAACTCCTA
GCCGCTTGTTTTGCTCGCAGCCGGTCTGGAGCAAACATTCTCGGGACGGATAACTCTGTT
GTTCTCTCCCGCAAATATACGTCGTTTCCATGGCTGCTAGGCTGTGCTGCCAACTGGATC
CTGCGCGGGACGTCCTTTGTTTACGTCCCGTCGGCGCTGAATCCCGCGGACGACCCTTCT
CGGGGCCGCTTGGGACTCTCTCGTCCCCTTCTCCGTCTGCCGTTTCGACCGACCACGGGG
CGCACCTCTCTTTACGCGGACTCCCCGTCTGTGCCTTCTCATCTGCCGGACCGTGTGCAC
TTCGCTTCACCTCTGCACGTCGCATGGAGACCACCGTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID Not Available
Target 1 GenAtlas ID Not Available
Target 1 HGNC ID Not Available
Target 1 Chromosome Location Not Available
Target 1 Locus Not Available
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Tong SP, Li JS, Vitvitski L, Trepo C: Active hepatitis B virus replication in the presence of anti-HBe is associated with viral variants containing an inactive pre-C region. Virology. 1990 Jun;176(2):596-603. [PubMed Link Image]
Target 1 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.