Dolutegravir (GSK1349572)

製品コードS2667 バッチS266706

印刷

化学情報

Chemical Structure Synonyms GSK1349572,S/GSK1349572 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H19F2N3O5
分子量 419.38 CAS No. 1051375-16-6
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 84 mg/mL (200.29 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
in vitro

Dolutegravir (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, it inhibits recombinant HIV-1 integrase-catalyzed strand transfer with 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 of 0,51 nM, 0.71 nM and 2.2 nM, respectively. [2]

In vitro, it 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, this compound shows equivalent activity against two protease inhibitor-resistant viruses with EC50 of 0.36 nM and 0.37 nM, respectively. [2]
in vivo

Dolutegravir (GSK1349572), also known as 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.
特徴 A next-generation and two-metal-binding HIV integrase strand transfer inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ In vitro strand transfer assay
The inhibitory potencies of this compound 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.
細胞アッセイ 細胞株 MT-4
濃度 0 to 10 μM
反応時間 4 days or 5 days
実験の流れ

Dolutegravir (GSK1349572) is evaluated using MT-4 cells growing exponentially at a density of 500000 or 600000 /mL, which 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 this compound. 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].
動物実験 動物モデル C3H/HeJ mice
投薬量 50 mg/kg
投与方法 o.g.

参考

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

カスタマーフィードバック

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の高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

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
Reduction of CD8 T cell functionality but not inhibitory capacity by integrase inhibitors [ J Virol, 2022, JVI0173021] PubMed: 35019724

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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