PL-100 is a novel HIV-1 protease inhibitor (PI) with a favorable cross-resistance profile and high genetic barrier. PL-100, emerged as a specific and noncytotoxic PI that exhibited potent inhibition of HIV-1 protease and viral replication in vitro (Ki, ~36 pM, and EC50, ~16 nM, respectively).In addition, PL-100 retained excellent antiviral activity against almost all of PI-resistant viruses (a panel of 63 viral strains from PI-experienced patients) and its performance in this regard was superior to those of atazanavir, amprenavir, indinavir, lopinavir, nelfinavir, and saquinavir.In vitro metabolism in human and rat liver microsomes shows that PL-100 was more stable than lopinavir, saquinavir, indinavir.PL-100 did not inhibit CYP2C9 and CYP2D6 but did inhibit CYP3A4 in vitro, which suggest that PL-100 is both a substrate and an inhibitor of CYP3A4.Therefore PL-100 is a promising drug for the treatment of drug-resistant HIV disease.

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