GSK1349572 (Dolutegravir)

Catalog No.S2667 Batch:S266706

Print

Technical Data

Formula

C20H19F2N3O5
Molecular Weight 419.38 CAS No. 1051375-16-6
Solubility (25°C)* In vitro DMSO 84 mg/mL (200.29 mM)
Water Insoluble
Ethanol Insoluble
In Vivo (Add solvents to the product individually and in order.)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Dolutegravir 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.
Targets
HIV integrase
(Cell-free assay)
2.7 nM
In vitro

Dolutegravir (GSK1349572) shows a potent inhibitory effect on nine clinical isolates from Integrase inhibitor-naive HIV-2-infected patients with EC50 ranging from 0.2 nM to 1.4 nM.

In vitro, it inhibits recombinant HIV-1 Integrase-catalysed strand transfer with an IC50 of 2.7 nM. Furthermore, this compound 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 values of 0.51 nM, 0.71 nM, and 2.2 nM, respectively.

In vitro, it also 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 to 2.1 nM. Similarly to its activity against wild-type virus, it shows equivalent efficacy against two protease inhibitor-resistant viruses, with EC50 values of 0.36 nM and 0.37 nM, respectively.
In Vivo

Dolutegravir (GSK1349572), a first-line antiretroviral drug (ARV) used in combination therapy for HIV-1, inhibits MMP activity and has the potential to affect prenatal and postnatal neurodevelopment.
Features A next-generation and two-metal-binding HIV Integrase strand transfer inhibitor.

Protocol (from reference)

Kinase Assay:

[2]
  • In vitro strand transfer assay

    The inhibitory potencies of Dolutegravir (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 scintillation 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.
Cell Assay:

[2]
  • Cell Lines

    MT-4

  • Concentrations

    0 to 10 μM

  • Incubation Time

    4 days or 5 days

  • Method

    Exponentially growing MT-4 cells at a density of 500,000 or 600,000/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 Dolutegravir (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].
Animal Study:

[3]
  • Animal Models

    C3H/HeJ mice

  • Dosages

    50 mg/kg

  • Administration

    o.g.

References

  • https://pubmed.ncbi.nlm.nih.gov/20827161/
  • https://pubmed.ncbi.nlm.nih.gov/21115794/
  • https://pubmed.ncbi.nlm.nih.gov/34390469/

Customer Product Validation

Strand transfer was carried out with RSV IN(1-269) (4 uM) and GU320R(2 uM)in the presence of 50mM NDSB201. Increasing concentrations of STIs were added as indicated at the top; DTG(Dolutegravir) in lanes 3-5, MK-2048 in lanes 6-8, and RAL in lanes 9-11. No STI was present in lane 2, and lane 1 contains the molecular weight markers. Strand transfer products and ODN substrate are identified on the right. CHS, circular half-site; OC target and SC target, open circular and supercoiled target DNA, respectively.

Data from [ J Biol Chem , 2014 , 289(28), 19648-58 ]

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 (****).

Data from [ , , Antiviral Res, 2016, 134:236-243 ]

Comparison of the activity of dolutegravir (DTG), raltegravir (RAL), and elvitegravir (EVG) against wild-type HIV-2ROD9. The number of independent determinations (n) for each strain is shown below the x-axis. No cytotoxic effects were observed in dolutegravir-treated MAGIC-5A cultures at concentrations as high as 10,000 nM.

Data from [ , , Retrovirology, 2015, 10.1186/s12977-015-0146-8 ]

Sellecks GSK1349572 (Dolutegravir) Has Been Cited by 34 Publications

Timed chromatin invasion during mitosis governs prototype foamy virus integration site selection and infectivity [ Nucleic Acids Res, 2025, 53(10)gkaf449] PubMed: 40448500
Cognate antigen engagement induces HIV-1 expression in latently infected CD4+ T cells from people on long-term antiretroviral therapy [ Immunity, 2024, 57(12):2928-2944.e6] PubMed: 39612916
HMGB1 Expression Levels Correlate with Response to Immunotherapy in Non-Small Cell Lung Cancer [ Lung Cancer, 2024, 15:55-67] PubMed: 38741920
Overexpression of TRPV1 activates autophagy in human lens epithelial cells under hyperosmotic stress through Ca2+-dependent AMPK/mTOR pathway [ Int J Ophthalmol, 2024, 17(3):420-434] PubMed: 38721513
Biological and Structural Analyses of New Potent Allosteric Inhibitors of HIV-1 Integrase [ Antimicrob Agents Chemother, 2023, 67(7):e0046223] PubMed: 37310224
The Development and Validation of RP-HPLC Method for Lamivudine, Dolutegravir, and Tenfovir in Human Plasma [ Pharm Res-Dordr, 2023, 21-40] PubMed: None
DNA ultra-sensitive quantification, a technology for studying HIV unintegrated linear DNA [ Cell Rep Methods, 2023, 3(4):100443] PubMed: 37159665
Spectrum of Activity of Raltegravir and Dolutegravir Against Novel Treatment-Associated Mutations In HIV-2 Integrase: A Phenotypic Analysis Using An Expanded Panel of Site-Directed Mutants [ J Infect Dis, 2022, jiac037] PubMed: 35134180
Inhibition of Adipose Tissue Beiging by HIV Integrase Inhibitors, Dolutegravir and Bictegravir, Is Associated with Adipocyte Hypertrophy, Hypoxia, Elevated Fibrosis, and Insulin Resistance in Simian Adipose Tissue and Human Adipocytes [ Cells, 2022, 11(11)1841] PubMed: 35681536
In Vitro Susceptibility of HIV Isolates with High Growth Capability to Antiretroviral Drugs [ Int J Mol Sci, 2022, 23(23)15380] PubMed: 36499705

RETURN POLICY
Selleck Chemical’s Unconditional Return Policy ensures a smooth online shopping experience for our customers. If you are in any way unsatisfied with your purchase, you may return any item(s) within 7 days of receiving it. In the event of product quality issues, either protocol related or product related problems, you may return any item(s) within 365 days from the original purchase date. Please follow the instructions below when returning products.

SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.