A nucleoside reverse transcriptase inhibitor
EFdA is a nucleoside reverse transcriptase inhibitor (NRTI).1 It inhibits HIV-1 reverse transcriptase via multiple mechanisms. EFdA inhibits replication of the HIV-1 strain HIV-1 IIIb, the laboratory isolate HIV NL4-3, and the clinical isolate HIV-2 EHO in MT-4 cells (EC50s = 73, 50, and 98 pM, respectively).2 It is also active against drug-resistant HIV with EC50 values ranging from 0.23 to 23 nM in a multinuclear activation of a galactosidase indicator (MAGI) assay.3 EFdA (1 and 10 mg/kg per day) prevents infection with HIV JR-CSF in humanized mice.4
1.Michailidis, E., Huber, A.D., Ryan, E.M., et al.4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) inhibits HIV-1 reverse transcriptase with multiple mechanismsJ. Biol. Chem.289(35)24533-24548(2014) 2.Markowitz, M., and Sarafianos, S.G.4'-Ethynyl-2-fluoro-2'-deoxyadenosine, MK-8591: A novel HIV-1 reverse transcriptase translocation inhibitorCurr. Opin. HIV AIDS13(4)294-299(2018) 3.Kawamoto, A., Kodama, E., Sarafianos, S.G., et al.2'-deoxy-4'-C-ethynyl-2-halo-adenosines active against drug-resistant human immunodeficiency virus type 1 variantsInt. J. Biochem. Cell Biol.40(11)2410-2420(2008) 4.Stoddart, C.A., Galkina, S.A., Joshi, P., et al.Oral administration of the nucleoside EFdA (4'-ethynyl-2-fluoro-2'-deoxyadenosine) provides rapid suppression of HIV viremia in humanized mice and favorable pharmacokinetic properties in mice and the rhesus macaqueAntimicrob. Agents Chemother.59(7)4190-4198(2015)
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