Dolutegravir

Catalog No.S2667 Batch:S266702

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Technical Data

Formula

C20H19F2N3O5

Molecular Weight 419.38 CAS No. 1051375-16-6
Solubility (25°C)* In vitro DMSO 83 mg/mL (197.91 mM)
Water Insoluble
Ethanol Insoluble
* <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.)

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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 [2]
(Cell-free assay)
2.7 nM
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

Dolutegravir (DTG) is a first-line antiretroviral drug (ARV) used in combination therapy for HIV-1. It 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 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.

Cell Assay:

[2]

  • Cell lines

    MT-4

  • Concentrations

    0 to 10 μM

  • Incubation Time

    4 days or 5 days

  • Method

    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].

Animal Study:

[3]

  • Animal Models

    C3H/HeJ mice

  • Dosages

    50 mg/kg

  • Administration

    o.g.

Customer Product Validation

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

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

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

Selleck's Dolutegravir has been cited by 27 publications

Biological and Structural Analyses of New Potent Allosteric Inhibitors of HIV-1 Integrase [ Antimicrob Agents Chemother, 2023, 67(7):e0046223] PubMed: 37310224
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
Reduction of CD8 T cell functionality but not inhibitory capacity by integrase inhibitors [ J Virol, 2022, JVI0173021] PubMed: 35019724
Effects of Injection Volume and Route of Administration on Dolutegravir In Situ Forming Implant Pharmacokinetics [ Pharmaceutics, 2022, 14(3)615] PubMed: 35335991
Impact of combinations of clinically observed HIV integrase mutations on phenotypic resistance to integrase strand transfer inhibitors (INSTIs): a molecular study [ J Antimicrob Chemother, 2022, dkab498] PubMed: 35061879
Biodegradable polymeric solid implants for ultra-long-acting delivery of single or multiple antiretroviral drugs [ Int J Pharm, 2021, 605:120844] PubMed: 34216767
A new engineering process of biodegradable polymeric solid implants for ultra-long-acting drug delivery [ Int J Pharm X, 2021, 3:100068] PubMed: 33392498

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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.