JE-2147

JE-2147 is an experimental small molecule dipeptide-based HIV protease inhibitor containing allophenylnorstatine. It was designed to potently inhibit the HIV protease enzyme, showing strong activity against a wide spectrum of HIV strains, including both wild-type and drug-resistant clinical isolates of HIV-1 and HIV-2, as well as simian immunodeficiency virus. In vitro studies demonstrated that JE-2147 retains potency against multi-drug resistant strains where other available protease inhibitors fail, with IC50 values in the low nanomolar range (13–41 nM). The compound’s structure features a flexible P2′ moiety that contributes to its efficacy against mutant viruses and delays the emergence of resistance compared to earlier inhibitors. Structural studies have shown that its binding is enthalpically driven and involves close contact with key residues in the viral protease active site[2][3][5][9]. Despite promising preclinical results, clinical development for HIV infection was discontinued after phase I trials[7].