GSK1349572 (Dolutegravir)

製品コードS2667 バッチS266704

化学情報

	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	84 mg/mL (200.29 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	Dolutegravirは、cell-freeアッセイにおいてIC50が2.7 nMである2つの金属結合型HIV integrase阻害剤であり、raltegravir耐性の特徴的な変異体であるY143R、Q148K、N155H、G140S/Q148Hに対しては中程度の活性を示します。
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-catalyzed 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.
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
キナーゼアッセイ	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.
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	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].
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：

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

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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