|S2005||Raltegravir (MK-0518)||<1 mg/mL||88 mg/mL||<1 mg/mL|
|S2001||Elvitegravir (GS-9137, JTK-303)||<1 mg/mL||89 mg/mL||35 mg/mL|
|S2667||Dolutegravir (GSK1349572)||<1 mg/mL||83 mg/mL||<1 mg/mL|
|S1366||BMS-707035||<1 mg/mL||38 mg/mL||<1 mg/mL|
|S2765||MK-2048||<1 mg/mL||9 mg/mL||<1 mg/mL|
|S7766||Cabotegravir (GSK744, GSK1265744)||<1 mg/mL||38 mg/mL||<1 mg/mL|
|S4642||Dolutegravir Sodium||<1 mg/mL||0.2 mg/mL||<1 mg/mL|
|S4187||Salicylanilide||<1 mg/mL||43 mg/mL||18 mg/mL|
Raltegravir (MK-0518) is a potent integrase (IN) inhibitor for WT and S217Q PFV IN with IC50 of 90 nM and 40 nM in cell-free assays, respectively. It shows greater than 1000-fold selectivity for HIV-1 IN over several related Mg2+-dependent enzyme such as HCV polymerase, HIV reverse transcriptase, HIV RNaseH and human α-, β-, γ-polymerases.
a: HCV, hepatitis C virus; HBV, hepatitis B virus. B: PI, protease inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; IN, integrase inhibitor. c: n=3. d: The EC50 for samatasvir in the presence of 45% human serum was 25 pM.
Elvitegravir (GS-9137, JTK-303) is an HIV integrase inhibitor for HIV-1 IIIB, HIV-2 EHO and HIV-2 ROD with IC50 of 0.7 nM, 2.8 nM and 1.4 nM in cell-free assays, respectively.
PhA efflux in MDCKII-BCRP cells. Concentration-dependent inhibition of BCRP/ABCG2 by elvitegravir and vicriviroc. Each curve depicts one representative experiment of a series of three or four; each concentration was tested in 30000 cells.
Dolutegravir (GSK1349572) is a two-metal-binding HIV integrase inhibitor with IC50 of 2.7 nM in a cell-free assay, modest activity against raltegravir-resistant signature mutants Y143R, Q148K, N155H, and G140S/Q148H.
qPCR kinetics of 2-LTRc and integrated DNA forms during a single round of HIV replication in the presence of inhibitors. MT4cells were infected with HIV-1 in the absence (DMSO) or in the presence of 100 nM EFV, 500 nM RAL, 500 nM DTG, 10 μM RDS1611, 10 μM RDS1644, 10 μM RDS1823 added at the time of infection (black bar) or 16 h p.i. (grey bar). Samples were analyzed for (A) total viral DNA at 24 h and (B) 2-LTRc and (C) integrated viral DNA at 48 h. The graph represents the average and standard deviation of three independent experiments. Significant at: p value < 0.05 (*); p value < 0.01 (**); p value < 0.001 (***); p value < 0.0001 (****).
BMS-707035 is a specific HIV-I integrase (IN) inhibitor with IC50 of 15 nM. Phase 2.
MK-2048 is a potent inhibitor of integrase (IN) and INR263K with IC50 of 2.6 nM and 1.5 nM, respectively.
Cabotegravir (GSK744, GSK1265744) is a long-acting HIV integrase inhibitor against a broad range of HIV subtypes, and inhibits the HIV-1 integrase catalyzed strand transfer reaction with IC50 of 3.0 nM. Phase 2.
Dolutegravir is a HIV integrase inhibitor with IC50 of 2.7 nM.
Comparison of the activity of dolutegravir (DTG), raltegravir (RAL), and elvitegravir (EVG) against wild-type HIV-2ROD9. Values for RAL and EVG include data from two previously-published studies of HIV-2 from our group [14,15] plus additional determinations; all data were obtained using the single-cycle assay. Bars indicate mean 50% effective concentrations (EC50); the number of independent determinations (n) for each strain is shown below the x-axis. P values were obtained via analysis of variance (ANOVA) of log10-transformed EC50 values with Tukey’s post test (Prism v6.0). No cytotoxic effects were observed in dolutegravir-treated MAGIC-5A cultures at concentrations as high as 10,000 nM.
Salicylanilides are a group of compounds with a wide range of biological activities including antiviral potency, antibacterial (including antimycobacterial) and antifungal activities.