GSK1349572, a novel tricyclic-core containing inhibitor, has an IC50 of 2.7 nM against HIV-1 with a corresponding EC50s of 0.51 nM, 0.71 nM, and 2.2 nM in PBMCs, MT-4 cells, and PHIV assays, respectively. [1] Cytotoxic concentration (CC50) in unstimulated and stimulated PBMCs was 189 uM and 52 uM, which results in a selectivity index of 9400. Though similar in potency to first-generation integrase inhibitors, Raltegravir and Elvitegravir, GSK1349572 possesses and resistance profile that is markedly different. In cross-resistance profiling experiments, GSK1349572 showed efficacy against five non-nucleoside- and nucleoside- reverse transcriptase inhibitor-resistant viruses equal to that of wild-type virus (EC50 = 1.3 to 2.1 nM). Similarly, GSK1349572 was efficacious against two protease inhibitor-resistant viruses, again equivalent to activity against wild-type virus (EC50 = 0.36 and 0.37 nM).

In studies of clinical isolates from HIV-2-infected patients, the median EC50 value for GSK1349572 was found to be 0.8 nM. [2]