Dolutegravir-d5

Dolutegravir-d₅ is intended for use as an internal standard for the quantification of dolutegravir by GC- or LC-MS. Dolutegravir is a potent inhibitor of HIV integrase with an IC₅₀ value of 2.7 nM for HIV-1 integrase-catalyzed strand transfer in vitro.¹ It inhibits HIV-1 viral replication (EC₅₀ = 0.51 nM) in peripheral blood mononuclear cells (PBMCs). The cytotoxic concentration (CC₅₀) values for dolutegravir in unstimulated and stimulated PBMCs are 189 and 52 µM, respectively, resulting in a therapeutic index of at least 9,400. It prevents replication of several HIV-1 strains (EC₅₀s = 0.36-2.1 nM) that are resistant to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors and impairs their ability to infect CIP4 cells.^1,2 Formulations containing dolutegravir have been used to treat HIV-1 infection in humans.³

1.Kobyayshi, M., Yoshinaga, T., Seki, T., et al.In vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitorAntimicrob. Agents and Chemother.55(2)813-821(2011) 2.Hare, S.A., Smith, S.J., MÉtifiot , M., et al.Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572)Mol. Pharmacol.80(4)565-572(2011) 3.Venter, W.D.F., Clayden, P., and Serenata, C.The ADVANCE study: a groundbreaking trial to evaluate a candidate universal antiretroviral regimenCurr. Opin. HIV AIDS12(4)351-354(2017)