| Name | Dolutegravir |
| Description | Dolutegravir (GSK1349572) (IC50=2.7 nM), a two-metal-binding HIV integrase inhibitor, exhibits medium activity against raltegravir-resistant signature mutants Y143R, Q148K, N155H, and G140S/Q148H. |
| Cell Research | MT-4 cells growing exponentially at a density of 500000 or 600000 /mL are infected with HIV-1 strain IIIB at a viral multiplicity of infection of 0.001 or a 50% tissue culture infective dose of 4 to 10. The cells are then aliquoted to 96-well plates in the presence of varying concentrations of S/GSK1349572. After incubation for 4 or 5 days, antiviral activity is determined by a cell viability assay that either measured bioluminescence with a CellTiter-Glo luminescent reagent or measured absorbance at 560 and 690 nm using the yellow tetrazolium MTT reagent [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide]. (Only for Reference) |
| Kinase Assay | In vitro strand transfer assay: The inhibitory potencies of S/GSK1349572 and other INIs are measured in a strand transfer assay using recombinant HIV integrase. A complex of integrase and biotinylated preprocessed donor DNA-streptavidin-coated Acintillation proximity assay (SPA) beads is formed by incubating 2 μM purified recombinant integrase with 0.66 μM biotinylated donor DNA-4 mg/mL streptavidin-coated SPA beads in 25 mM sodium morpholinepropanesulfonic acid (MOPS) (pH 7.2), 23 mM NaCl, and 10 mM MgCl2 for 5 minutes at 37 °C. These beads are spun down and preincubated with diluted INIs for 60 minutes at 37 °C. Then a 3H-labeled target DNA substrate is added to give a final concentration of 7 nM substrate, and the strand transfer reaction mixture is incubated at 37 °C for 25 to 45 minutes, which allows for a linear increase in the strand transfer of donor DNA to radiolabeled target DNA. The signal is read using a Wallac MicroBeta scintillation plate reader. |
| In vitro | S/GSK1349572 shows the potent inhibitory effect on nine clinical isolates from integrase inhibitor-naive HIV-2-infected patients with EC50 ranging from 0.2 nM -1.4 nM. [1] In vitro, S/GSK1349572 inhibits recombinant HIV-1 integrase-catalyzed strand transfer with IC50 of 2.7 nM. Furthermore, S/GSK1349572 potently inhibits HIV replication in cells such as peripheral blood mononuclear cells (PBMCs), MT-4 cells and CIP4 cells infected with a self-inactivating PHIV lentiviral vector with EC50 of 0,51 nM, 0.71 nM and 2.2 nM, respectively. [2] In vitro, S/GSK1349572 exhibits potent activity against five different nonnucleoside reverse transcription inhibitor--resistant or nucleoside reverse transcription inhibitor--resistant viruses with EC50 ranging from 1.3 nM -2.1 nM. Similarly to that against wild-type virus, S/GSK1349572 shows equivalent activity against two protease inhibitor-resistant viruses with EC50 of 0.36 nM and 0.37 nM, respectively. [2] |
| In vivo | Following a single intravenous (IV) administration, Dolutegravir demonstrates low plasma clearance in rats (0.23 mL/min/kg) and monkeys (2.12 mL/min/kg), with a half-life of approximately 6 hours and a low steady-state volume of distribution (VSS). When orally administered as a solution to fasted male rats and a single monkey, Dolutegravir is rapidly absorbed, showing high oral bioavailability (75.6% and 87.0%, respectively). Dolutegravir exposure, assessed by peak concentration (Cmax) and area under the curve (AUC), increases with dose escalation in oral suspension forms up to 250 mg/kg in non-fasted rats and 50 mg/kg in non-fasted monkeys, albeit with a less than proportional increase[3]. |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility Information | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 65 mg/mL (154.99 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| Keywords | GSK 1349572 | HIV Integrase | GSK-1349572 | HIV | inhibit | S/GSK-1349572 | Dolutegravir | S/GSK 1349572 | Human immunodeficiency virus | Inhibitor |
| Inhibitors Related | Stavudine | 5-Fluorouracil | Emtricitabine | Kaempferol | Dolutegravir intermediate-1 | Dextran sulfate sodium salt (MW 4500-5500) | Lamivudine | Chloroquine phosphate | Decanedioic acid | Tenofovir |
| Related Compound Libraries | FDA-Approved & Pharmacopeia Drug Library | Bioactive Compound Library | EMA Approved Drug Library | Drug Repurposing Compound Library | Anti-Viral Compound Library | Inhibitor Library | FDA-Approved Drug Library | Bioactive Compounds Library Max | Anti-COVID-19 Compound Library | Human Metabolite Library |
United States
