JE-2147

JE-2147 (AG1776) is a potent dipeptide protease inhibitor with a Ki of 0.33 nM for HIV-1 protease. JE-2147 has effective activities against a wide spectrum of HIV-1, HIV-2, simian immunodeficiency virus, and various clinical HIV-1 strains in vitro[1][2].

Signaling Pathways >> Anti-infection >> HIV

Research Areas >> Infection

Signaling Pathways >> Metabolic Enzyme/Protease >> HIV Protease

IC50: 44 nM [HIV-1LAI (SI)], 24 nM [HIV-1Ba-L (SI)], 35 nM [HIV-1LAI (NSI)], 47 nM [HIV-2EHO (SI)][1] Ki:0.33 nM (HIV-1 protease)[2]

JE-2147 (0.01-0.05 μM; 7 days; PBMC and MT-2 cells) exhibits highly potent antiviral activity against HIV-1 with IC50s of 44 nM, 24 nM, 35 nM and 47 nM for HIV-1LAI (SI), HIV-1Ba-L (SI), HIV-1LAI (NSI) and HIV-2EHO (SI), respectively[1]. JE-2147 is effective against the replication of HIV-1 IIIB in various cells (T cell, B cell, macrophage, and PBMC) with IC50 values ranging from 31 to 160 nM and also had antiviral activity against simian immunodefidiency virus and HIV-2[2].

JE-2147 exhibits good oral bioavailability and plasma pharmacokinetic profiles in dogs and rats[2]. Pharmacokinetic Parameters of JE-2147 in beagle dogs and male Sprague-Dawley rats[2]. Sprague-Dawley rats Beagle dogs i.v., 10 mg/kg i.d., 10 mg/kg i.v., 25 mg/kg p.o.(fed), 25 mg/kg p.o.(fasted), 25 mg/kg t1/2β (min) 93 / 94 / / Cmax (μM) / 0.70 ± 0.20 / 4.02 ± 0.72 5.30 ± 1.13 Tmax (min) / 60 / 90 60 F (%) / 41.6 ± 10.7 / 32.6 ± 0.06 37.1 ± 0.08 CL (L/h/kg) / / 0.88 ± 0.09 / / Vd, ss (L/kg) / / 1.58 / / AUC0-24 (μM·min) / / / 1009 1149 Animal Model: Beagle dogs and male Sprague-Dawley rats[2] Dosage: 25 mg/kg for dogs; 10 mg/kg for rats Administration: i.v. and i.d. for rats; i.v. and p.o. for dogs. Result: Exhibited favorable pharmacokinetic properties.