受注:045-509-1970 |
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Synonyms | GSK1349572,S/GSK1349572 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C20H19F2N3O5 |
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分子量 | 419.38 | CAS No. | 1051375-16-6 | |
Solubility (25°C)* | 体外 | DMSO | 83 mg/mL warmed with 50ºC water bath (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. |
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. |
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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. |
特徴 | A next-generation and two-metal-binding HIV integrase strand transfer inhibitor. |
キナーゼアッセイ | In vitro strand transfer assay | |
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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. | ||
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 | 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]. |
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動物実験 | 動物モデル | C3H/HeJ mice |
投薬量 | 50 mg/kg | |
投与方法 | o.g. |
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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]
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 |
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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