Adefovir-d4 (Synonyms: PMEA-d4)

Adefovir-d₄ is intended for use as an internal standard for the quantification of adefovir by GC- or LC-MS. Adefovir is an active metabolite of the antiviral nucleoside analog adefovir dipivoxil .¹ Adefovir is formed from adefovir dipivoxil by gastrointestinal carboxylesterase 2 (CES2).² It inhibits cytopathogenicity induced by herpes simplex virus 1 (HSV-1) and HSV-2 (EC₅₀ = 7 µg/ml for both in E₆SM cells), HIV-1 and HIV-2 (EC₅₀s = 1.8 and 2.5 µg/ml, respectively, in CEM cells), and varicella zoster virus (VZV; EC₅₀ = 10 µg/ml in human embryonic lung fibroblasts).³ Adefovir (50 mg/kg, p.o.) reduces increases in lymph node viral DNA and serum IgG levels in a mouse model of AIDS induced by infection with the retroviral complex LP-BM5.⁴ It also inhibits tumor growth induced by Moloney sarcoma virus (MSV) infection in mice at the same dose.⁵

1.Arimilli, M.N., Dougherty, J.P., Cundy, K.C., et al.Orally bioavailable acyclic nucleoside phosphonate prodrugs: Adefovir dipivoxil and bis(POC)PMPAAdvances in Antiviral Drug Design369-91(1999) 2.Laizure, S.C., Herring, V., Hu, Z., et al.The role of human carboxylesterases in drug metabolism: Have we overlooked their importance•Pharmacotherapy33(2)210-222(2013) 3.HolÝ, A., Votruba, I., MasojÍdkovÁ, M., et al.6-[2-(Phosphonomethoxy)alkoxy]pyrimidines with antiviral activityJ. Med. Chem.45(9)1918-1929(2002) 4.Rossi, L., Dominici, S., Serafini, S., et al.Pharmacokinetic and antiretroviral activity in mice of oral [P1,P2-bis[2-(adenin-9-yl)ethoxymethyl]phosphonate], a prodrug of 9-(2-phosphonylmethoxyethyl)adenineJ. Antimicrob. Chemother.50(3)365-374(2002) 5.Naesens, L., Balzarini, J., Bischofberger, N., et al.Antiretroviral activity and pharmacokinetics in mice of oral bis(pivaloyloxymethyl)-9-(2-phosphonylmethoxyethyl)adenine, the bis(pivaloyloxymethyl) ester prodrug of 9-(2-phosphonylmethoxyethyl)adenineAntimicrob. Agents Chemother.40(1)22-28(1996)