GSK1349572 (Dolutegravir)

製品コードS2667 バッチS266706

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：

Ultra-long-actingremovabledrugdeliverysystemforHIVtreatmentandprevention [ NatureCommunications, October8, 2018, 4156]
ActivationofPERK-ATF4-CHOPpathwayasanoveltherapeuticapproachforefficienteliminationofHTLV-1-infectedcells [ BloodAdvances, May12, 2020, 1845-1858]
EffectsofInjectionVolumeandRouteofAdministrationonDolutegravirInSituFormingImplantPharmacokinetics [ Pharmaceutics, March11, 2022, 615]
Invitroactivityofdolutegraviragainstwild-typeandintegraseinhibitor-resistantHIV-2 [ Retrovirology, February5, 2015, 10]
ExvivoantiretroviralpotencyofnewerintegrasestrandtransferinhibitorscabotegravirandbictegravirinHIV-1non-Bsubtypes [ AIDS, February20, 2018, 469-476]
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

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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