Adefovir Dipivoxil

Adefovir Dipivoxil is a acyclic nucleotide analog reverse transcriptase inhibitor (ntRTI). It 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.

Designed for biological research and industrial applications, not intended for individual clinical or medical purposes.

CAT No: 10-101-107

CAS No:142340-99-6

Synonyms/Alias:Adefovir di(pivaloyloxymethyl) ester;Bis(POM)PMEA; GS-0840; Piv2PMEA;9-[2-(Bis[(pivaloyloxy)-methoxy]phosphinylmethoxy)ethyl]adenine

Chemical Name:[2-(6-aminopurin-9-yl)ethoxymethyl-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate

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M.F/Formula
C20H32N5O8P
M.W/Mr.
501.48
Sequence
no
Labeling Target
DNA polymerase/reverse transcriptase
Application
For treatment of hepatitis B and herpes simplex virus infection
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Biological Activity
Adefovir Dipivoxil is a dipivoxil formulation of adefovir, a nucleoside reverse transcriptase inhibitor analog of adenosine with activity against hepatitis B virus (HBV), herpes virus, and human immunodeficiency virus (HIV).
Areas of Interest
Infection
Functions
Rna-dna hybrid ribonuclease activity
Target
HBV

Adefovir Dipivoxil is a nucleotide analog prodrug widely recognized for its role in molecular biology and biochemical research. Characterized by its ability to inhibit viral DNA polymerase, this compound undergoes intracellular conversion to its active metabolite, which then interferes with the replication processes of DNA viruses. Its chemical structure allows for efficient cellular uptake and subsequent phosphorylation, making it a valuable tool in studies exploring nucleotide metabolism, polymerase inhibition, and antiviral mechanisms. Researchers appreciate its stability and bioavailability in in vitro systems, enabling precise control over experimental variables in a range of investigative contexts. The versatility of Adefovir Dipivoxil has led to its adoption in various research applications, particularly those focusing on viral replication pathways and nucleic acid synthesis.

Antiviral Research: In the field of antiviral research, Adefovir Dipivoxil serves as a critical agent for dissecting the mechanisms by which nucleotide analogs inhibit viral DNA polymerases. Scientists utilize it to model the inhibition of viral replication in cell-based assays, providing insights into the molecular events that underlie polymerase stalling and chain termination. Its use enables the evaluation of resistance mutations, the assessment of polymerase fidelity, and the identification of potential escape pathways, all of which are essential for developing next-generation antiviral strategies.

Viral Genome Replication Studies: The compound is frequently employed in studies examining viral genome replication. By introducing the prodrug into cultured cells infected with DNA viruses, researchers can monitor the effects of its active metabolite on the synthesis of viral genomes. This approach allows for detailed analysis of replication intermediates, the identification of host factors involved in viral DNA synthesis, and the exploration of potential co-factors that modulate the efficacy of nucleotide analogs. Such investigations are fundamental to understanding the life cycle of DNA viruses and the points at which therapeutic intervention may be most effective.

Drug Resistance Mechanism Elucidation: Adefovir Dipivoxil is also instrumental in elucidating the molecular mechanisms underlying drug resistance. In laboratory models, it is used to select for resistant viral strains, which are then characterized at the genetic and biochemical levels. This process reveals the specific mutations that confer reduced susceptibility to nucleotide analogs, thereby informing the design of new compounds that can overcome resistance. Additionally, these studies shed light on the evolutionary dynamics of viral populations under selective pressure, enhancing our understanding of viral adaptation.

Pharmacokinetics and Metabolism Research: The prodrug nature of Adefovir Dipivoxil makes it an ideal candidate for investigations into drug activation, distribution, and metabolism. Researchers employ it to study the enzymatic pathways responsible for prodrug conversion, the kinetics of intracellular phosphorylation, and the stability of active metabolites. These experiments provide valuable data on drug bioavailability, cellular uptake, and the factors influencing therapeutic efficacy in experimental systems. Such pharmacokinetic studies are crucial for optimizing dosing regimens and improving the design of future nucleotide analogs.

Combination Therapy Evaluation: In the context of combination therapy research, Adefovir Dipivoxil is often assessed alongside other nucleotide or nucleoside analogs to determine potential synergistic or antagonistic effects. Scientists use it in co-treatment protocols to evaluate how different agents interact at the molecular level, examining their collective impact on viral replication and the emergence of resistance. These studies inform the rational design of multi-drug regimens and contribute to a deeper understanding of combination strategies in antiviral therapy development.

Biochemical Assay Development: The utility of Adefovir Dipivoxil extends to the development of biochemical assays aimed at screening for polymerase inhibitors or characterizing enzyme kinetics. Its well-defined mechanism of action and predictable cellular processing make it a reliable reference compound in assay validation. By incorporating it into high-throughput screening platforms, researchers can benchmark the activity of novel compounds and establish robust protocols for identifying new antiviral candidates. This application supports the ongoing search for innovative therapeutics and enhances the toolkit available for molecular virology research.

Source#
Synthetic
Long-term Storage Conditions
Soluble in DMSO
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Short-term Storage Conditions
Dry, dark and at 0 - 4 °C
Solubility
-20 °C
Organism
HBV-D
InChI
InChI=1S/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)
InChI Key
WOZSCQDILHKSGG-UHFFFAOYSA-N
Canonical SMILES
CC(C)(C)C(=O)OCOP(=O)(COCCN1C=NC2=C(N=CN=C21)N)OCOC(=O)C(C)(C)C
BoilingPoint
641.0±65.0 °C at 760 mmHg
References

Tenofovir disoproxil fumarate (DF) is a nucleotide analogue and a potent inhibitor of human immunodeficiency virus type 1 reverse transcriptase and hepatitis B virus (HBV) polymerase.

Marcellin P, Heathcote E J, Buti M, et al. Tenofovir disoproxil fumarate versus adefovir dipivoxil for chronic hepatitis B[J]. New England Journal of Medicine, 2008, 359(23): 2442-2455.

Adefovir dipivoxil possesses potent in vitro and in vivo antiviral activity in wild-type hepatitis B. This study assessed the safety and efficacy of adefovir dipivoxil alone and in combination with lamivudine compared with ongoing lamivudine therapy in patients with chronic hepatitis B with compensated liver disease and lamivudine-resistant hepatitis B virus (HBV).

Peters M G, Hann H W, Martin P, et al. Adefovir dipivoxil alone or in combination with lamivudine in patients with lamivudine-resistant chronic hepatitis B[J]. Gastroenterology, 2004, 126(1): 91-101.

Adefovir dipivoxil effectively inhibits both hepatitis B virus (HBV) replication and disease activity in patients with chronic hepatitis B. Resistance to treatment was not observed in 2 recent large placebo-controlled 48-week studies with this drug. The aim of this study was to characterize adefovir resistance in a patient who developed clinical and virologic evidence of breakthrough during a 96-week course of treatment.

Angus P, Vaughan R, Xiong S, et al. Resistance to adefovir dipivoxil therapy associated with the selection of a novel mutation in the HBV polymerase[J]. Gastroenterology, 2003, 125(2): 292-297.

Oral adefovir dipivoxil is effective and generally well tolerated in HBeAg-positive and -negative patients chronically infected with wild-type or lamivudine-resistant HBV. Few resistant HBV mutants have emerged to date. Data from ongoing long-term studies are awaited with interest. Existing treatment options for patients with chronic hepatitis B are limited in both number and effectiveness; the proven efficacy, good tolerability profile and apparently low potential for resistance of adefovir dipivoxil make it a promising new option in the management of this disease.

Dando T M, Plosker G L. Adefovir dipivoxil: a review of its use in chronic hepatitis B[J]. Drugs, 2003, 63(20): 2215-2235.

Melting Point
98-102ºC

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