GRL-09510, a Unique P2-Crown-Tetrahydrofuranylurethane -Containing HIV-1 Protease Inhibitor, Maintains Its Favorable Antiviral Activity against Highly-Drug-Resistant HIV-1 Variants in vitro.

ABSTRACT: We report that GRL-09510, a novel HIV-1 protease inhibitor (PI) containing a newly-generated P2-crown-tetrahydrofuranylurethane (Crwn-THF), a P2'-methoxybenzene, and a sulfonamide isostere, is highly active against laboratory and primary clinical HIV-1 isolates (EC₅₀: 0.0014-0.0028 μM) with minimal cytotoxicity (CC₅₀: 39.0 μM). Similarly, GRL-09510 efficiently blocked the replication of HIV-1_NL4-3 variants, which were capable of propagating at high-concentrations of atazanavir, lopinavir, and amprenavir (APV). GRL-09510 was also potent against multi-drug-resistant clinical HIV-1 variants and HIV-2_ROD. Under the selection condition, where HIV-1_NL4-3 rapidly acquired significant resistance to APV, an integrase inhibitor raltegravir, and

SUBMITTER: Amano M 

PROVIDER: S-EPMC5613016 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature