Réactifs et instruments pour l'immunologie, la biologie cellulaire et la biologie moléculaire.
 
> Dolutegravir [1051375-16-6]

Dolutegravir [1051375-16-6]

Imprimer Imprimer
Identifiez-vous

Référence HY-13238-10mg

Conditionnement : 10mg

Marque : MedChemExpress

Demander plus d'informations

Contactez votre distributeur local :


Téléphone : +1 850 650 7790

Dolutegravir (S/GSK1349572) is a highly potent and orally bioavailable HIV integrase strand transfer inhibitor with an IC50 of 2.7 nM for HIV-1 integrase-catalyzed strand transfer. Dolutegravir (S/GSK1349572) inhibits HIV-1 viral replication with an IC50 of 0.51 nM in peripheral blood mononuclear cells. Dolutegravir retains a high potency against the HIV-1 Y143R, N155H, and G140S/Q148H mutants (EC50=3.6-5.8 nM).

Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.

Dolutegravir Chemical Structure

Dolutegravir Chemical Structure

CAS No. : 1051375-16-6

Size Prix Stock Quantité
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
 En stock
Solution
10 mM * 1 mL in DMSO En stock
Solid
2 mg En stock
5 mg En stock
10 mg En stock
50 mg En stock
100 mg En stock
200 mg En stock
500 mg En stock
1 g En stock
5 g   Obtenir un devis  
10 g   Obtenir un devis  
or Bulk Inquiry

* Veuillez sélectionner la quantité avant d'ajouter des articles.

This product is a controlled substance and not for sale in your territory.

Based on 26 publication(s) in Google Scholar

Other Forms of Dolutegravir:

  • Cabotegravir In-stock
  • Dolutegravir sodium In-stock
  • Dolutegravir-d6 Obtenir un devis
  • Dolutegravir-d3 Obtenir un devis
  • Dolutegravir-d5 Obtenir un devis
  • Dolutegravir (Standard) Obtenir un devis

    Dolutegravir purchased from MedChemExpress. Usage Cited in: Antivir Ther. 2017;22(8):645-657.  [Abstract]

    Dolutegravir (DTG) and MVC+DTG significantly increase the SIRT1 level by respectively, 9% and 18%.

    Dolutegravir purchased from MedChemExpress. Usage Cited in: Cell Physiol Biochem. 2016 Jul 21;39(2):639-650.  [Abstract]

    Arithmetic means±SEM (n=19) of erythrocyte annexin-V-binding following incubation for 48 hours to Ringer solution without (white bar) or with (black bars) Dolutegravir (4.77-19.08 µM). For comparison, the effect of the solvent DMSO is shown (grey bar).
    Description

    Dolutegravir (S/GSK1349572) is a highly potent and orally bioavailable HIV integrase strand transfer inhibitor with an IC50 of 2.7 nM for HIV-1 integrase-catalyzed strand transfer. Dolutegravir (S/GSK1349572) inhibits HIV-1 viral replication with an IC50 of 0.51 nM in peripheral blood mononuclear cells. Dolutegravir retains a high potency against the HIV-1 Y143R, N155H, and G140S/Q148H mutants (EC50=3.6-5.8 nM)[1][2].

    IC50 & Target

    HIV-1

     

    Cellular Effect
    Cell Line Type Value Description References
    CHO IC50
    > 100 μM
    Compound: DTG, S/GSK1349572, Dolutegravir
    Inhibition of human OATP1B1 expressed in CHO cells using [3H]estradiol 17beta-D-glucuronide as substrate by liquid scintillation counting analysis
    Inhibition of human OATP1B1 expressed in CHO cells using [3H]estradiol 17beta-D-glucuronide as substrate by liquid scintillation counting analysis
    		[PMID: 23132334]
    HEK293 IC50
    > 100 μM
    Compound: DTG, S/GSK1349572, Dolutegravir
    Inhibition of human OATP1B3 expressed in BacMam baculovirus virus infected HEK MSR2 cells using [3H]estradiol 17beta-D-glucuronide as substrate by liquid scintillation counting analysis
    Inhibition of human OATP1B3 expressed in BacMam baculovirus virus infected HEK MSR2 cells using [3H]estradiol 17beta-D-glucuronide as substrate by liquid scintillation counting analysis
    		[PMID: 23132334]
    HEK-293T IC50
    1.7 nM
    Compound: 3, DTG, S/GSK572, S/GSK1349572, Dolutegravir
    Antiviral activity against pseudo Human immunodeficiency virus infected in HEK293T cells after 2 days
    Antiviral activity against pseudo Human immunodeficiency virus infected in HEK293T cells after 2 days
    		[PMID: 23845180]
    HEK-293T IC50
    22 nM
    Compound: 3, DTG, S/GSK572, S/GSK1349572, Dolutegravir
    Antiviral activity against pseudo Human immunodeficiency virus infected in HEK293T cells after 2 days in presence of human serum albumin
    Antiviral activity against pseudo Human immunodeficiency virus infected in HEK293T cells after 2 days in presence of human serum albumin
    		[PMID: 23845180]
    HOS EC50
    1.6 nM
    Compound: 2, DTG
    Antiviral activity against HIV-1 harboring wild type integrase infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay
    Antiviral activity against HIV-1 harboring wild type integrase infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay
    		[PMID: 24901667]
    HOS EC50
    11 nM
    Compound: 2, DTG
    Antiviral activity against INSTI-resistant HIV-1 harboring integrase R263K mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay
    Antiviral activity against INSTI-resistant HIV-1 harboring integrase R263K mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay
    		[PMID: 24901667]
    HOS EC50
    13 nM
    Compound: 2, DTG
    Antiviral activity against INSTI-resistant HIV-1 harboring integrase G118R mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay
    Antiviral activity against INSTI-resistant HIV-1 harboring integrase G118R mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay
    		[PMID: 24901667]
    HOS EC50
    3.6 nM
    Compound: 2, DTG
    Antiviral activity against raltegravir-resistant HIV-1 harboring integrase N155H mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay
    Antiviral activity against raltegravir-resistant HIV-1 harboring integrase N155H mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay
    		[PMID: 24901667]
    HOS EC50
    4.3 nM
    Compound: 2, DTG
    Antiviral activity against raltegravir-resistant HIV-1 harboring integrase Y143R mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay
    Antiviral activity against raltegravir-resistant HIV-1 harboring integrase Y143R mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay
    		[PMID: 24901667]
    HOS EC50
    5.8 nM
    Compound: 2, DTG
    Antiviral activity against raltegravir-resistant HIV-1 harboring integrase G140S/Q148H double mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay
    Antiviral activity against raltegravir-resistant HIV-1 harboring integrase G140S/Q148H double mutant infected in human HOS cells pretreated with compound for 3 hrs by single-round HIV-1 infectivity assay
    		[PMID: 24901667]
    MDCK-II IC50
    > 100 μM
    Compound: DTG, S/GSK1349572, Dolutegravir
    Inhibition of MDR1 (unknown origin) expressed in MDCK2 cells assessed as basolateral to apical transport of [3H]digoxin after 90 mins by liquid scintillation counting analysis
    Inhibition of MDR1 (unknown origin) expressed in MDCK2 cells assessed as basolateral to apical transport of [3H]digoxin after 90 mins by liquid scintillation counting analysis
    		[PMID: 23132334]
    MDCK-II IC50
    > 30 μM
    Compound: DTG, S/GSK1349572, Dolutegravir
    Inhibition of BCRP (unknown origin) expressed in MDCK2 cells assessed as basolateral to apical transport of [14C]cimetidine after 90 mins by liquid scintillation counting analysis
    Inhibition of BCRP (unknown origin) expressed in MDCK2 cells assessed as basolateral to apical transport of [14C]cimetidine after 90 mins by liquid scintillation counting analysis
    		[PMID: 23132334]
    MDCK-II IC50
    1.9 μM
    Compound: DTG, S/GSK1349572, Dolutegravir
    Inhibition of human OCT2 expressed in MDCK2 cells using [14C]metformin as substrate by liquid scintillation counting analysis
    Inhibition of human OCT2 expressed in MDCK2 cells using [14C]metformin as substrate by liquid scintillation counting analysis
    		[PMID: 23132334]
    MT4 IC50
    2 nM
    Compound: 3, DTG, S/GSK572, S/GSK1349572, Dolutegravir
    Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT4 cells after 4 to 5 days by bioluminescence assay
    Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT4 cells after 4 to 5 days by bioluminescence assay
    		[PMID: 23845180]
    Sf9 IC50
    > 100 μM
    Compound: DTG, S/GSK1349572, Dolutegravir
    Inhibition of human MRP2 expressed in baculovirus-infected Sf9 cell membrane vesicle using [3H]estradiol 17beta-D-glucuronide as substrate preincubated with vesicles for 5 mins prior to substrate addition by liquid scintillation counting analysis
    Inhibition of human MRP2 expressed in baculovirus-infected Sf9 cell membrane vesicle using [3H]estradiol 17beta-D-glucuronide as substrate preincubated with vesicles for 5 mins prior to substrate addition by liquid scintillation counting analysis
    		[PMID: 23132334]
    Vero C1008 CC50
    > 40 μM
    Compound: Dolutegravir
    Cytotoxicity (CC50) determination in Vero E6 cells measured by fluorescence (OD590nm)
    Cytotoxicity (CC50) determination in Vero E6 cells measured by fluorescence (OD590nm)
    		10.1101/2020.04.03.023846
    Vero C1008 EC50
    22.04 μM
    Compound: Dolutegravir
    Antiviral efficacy against SARS-CoV-2 (strain BavPat1) in Vero E6 cells assessed by inhibition of viral RNA replication measured by RT-PCR after 2 days
    Antiviral efficacy against SARS-CoV-2 (strain BavPat1) in Vero E6 cells assessed by inhibition of viral RNA replication measured by RT-PCR after 2 days
    		10.1101/2020.04.03.023846
    In Vitro

    The EC50 of Dolutegravir (S/GSK1349572) against HIV-1 is 0.51 nM in PBMCs, 0.71 nM in MT-4 cells, and 2.2 nM in the PHIV assay, which uses a pseudotyped self-inactivating virus. The 50% cytotoxic concentrations (CC50) for Dolutegravir in proliferating IM-9, U-937, MT-4, and Molt-4 cells are 4.8, 7.0, 14, and 15 μM, respectively. In unstimulated and stimulated PBMCs, the CC50 are 189 μM and 52 μM, respectively. Based on the EC50 of Dolutegravir against HIV-1 in PBMCs (i.e., 0.51 nM), this translates to a cell-based therapeutic index of at least 9,400[1].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

    Dolutegravir Related Antibodies
    In Vivo

    Following a single intravenous (IV) administration of Dolutegravir, the plasma clearance is low in rats (0.23 mL/min/kg) and monkeys (2.12 mL/min/kg). The half-lives in the rat and monkey are similar, approximately 6 h, and the steady-state volume of distribution (VSS) is low. Following oral administration, Dolutegravir is rapidly absorbed with a high oral bioavailability when administered as a solution to fasted male rats and a single monkey (75.6 and 87.0%, respectively). Dolutegravir exposure (Cmax and AUC) increased with increasing dose following oral administration of a suspension to non-fasted rats up to 250 mg/kg and non-fasted monkeys up to 50 mg/kg, although the increase is less than proportional[3].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
    Essai clinique
    Masse moléculaire

    419.38

    Formule

    C20H19F2N3O5
    CAS No.

    1051375-16-6

    Appearance

    Solid

    Color

    White to off-white

    SMILES

    FC1=CC(F)=C(C=C1)CNC(C2=CN(C3=C(C2=O)O)C[C@@](18)(N4C3=O)OCC[C@H]4C)=O
    Livraison

    Room temperature in continental US; may vary elsewhere.
    Stockage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 1 year
    -20°C 6 months
    Solvant et solubilité
    In Vitro: 

    DMSO : 10 mg/mL (23.84 mM; Need ultrasonic and warming; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.3845 mL 11.9224 mL 23.8447 mL
    5 mM 0.4769 mL 2.3845 mL 4.7689 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

    • Calculateur de molarité

    • Calculateur de dilution

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

    Mass
    =
    Concentration
    ×
    Volume
    ×
    Molecular Weight *

    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

    C1

    ×
    Volume (start)

    V1

    =
    Concentration (final)

    C2

    ×
    Volume (final)

    V2

    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 1

      Add each solvent one by one:  5% DMSO    95% (20% SBE-β-CD in Saline)

      Solubility: ≥ 2.62 mg/mL (6.25 mM); Clear solution

    • Protocol 2

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

      Solubility: ≥ 2.5 mg/mL (5.96 mM); Clear solution

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

    Animal weight
    (per animal)

    g

    Dosing volume
    (per animal)

    μL

    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Pureté et documentation

    Purity: 99.98%

    SDS (398 KB)

    COA (248 KB) LCMS (93 KB)

    Instruction de manipulation (2659 KB)
    Références

    • [1]. Kobayashi M, et al. In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother. 2011 Feb;55(2):813-21.  [Content Brief]

      [2]. Hare S, et al. Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol. 2011 Oct;80(4):565-72.  [Content Brief]

      [3]. Moss L, et al. The comparative disposition and metabolism of dolutegravir, a potent HIV-1 integrase inhibitor, in mice, rats, and monkeys. Xenobiotica. 2015 Jan;45(1):60-70.  [Content Brief]

    Test cellulaire
    [1]

    In vitro growth inhibition (cytotoxicity) studies are conducted with S/GSK1349572 (0.16, 0.8, 4, and 20 nM) in proliferating human leukemic and lymphomic cell lines (IM-9, U-937, MT-4, and Molt-4) as well as in stimulated and unstimulated human PBMCs. ATP levels are quantified by using the CellTiter-Glo luciferase reagent to measure the ability of a compound to inhibit cell growth as an indicator of the compound's potential for cytotoxicity[1].

    MCE n'a pas confirmé de manière indépendante l'exactitude de ces méthodes. Ils sont pour référence seulement.
    Administration animale
    [2]

    For rat and monkey PK studies, Dolutegravir is administered as the free acid or the sodium salt. All doses are presented in terms of the free acid. Dolutegravir is administered by intravenous (IV) short-term (within 2 min) bolus (1 mg/kg) to three male rats and two male monkeys. For single oral administration, Dolutegravir as a solution (5 mg/kg) is administered to three fasted male rats and two fasted male monkeys. Dolutegravir is administered as single oral doses of 5, 50, 100, and 250 mg/kg to non-fasted male rats (n=2/dose level) and 3, 10, and 50 mg/kg to non-fasted female monkeys. For intravenous administration, blood samples are collected from rats (0.2 mL via jugular vein cannula) and monkeys (approximately 0.2 or 0.5 mL via saphenous vein in a hindlimb) into Na2EDTA-treated syringes at 0.083, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 h. For oral administration, samples are collected at 0.25 (rats only), 0.5, 1, 2, 4, 6 [rats (solution and suspension) and monkey (solution only)], 8, and 24 h. Following collection, the blood is immediately put on wet ice and then centrifuged within an hour at 1740 g for 10 min at 4°C to obtain plasma. All samples are stored at approximately -20°C or colder prior to analysis by using a method based on protein precipitation and LC-MS/MS analysis.

    MCE n'a pas confirmé de manière indépendante l'exactitude de ces méthodes. Ils sont pour référence seulement.
    Références

    • [1]. Kobayashi M, et al. In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother. 2011 Feb;55(2):813-21.  [Content Brief]

      [2]. Hare S, et al. Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol. 2011 Oct;80(4):565-72.  [Content Brief]

      [3]. Moss L, et al. The comparative disposition and metabolism of dolutegravir, a potent HIV-1 integrase inhibitor, in mice, rats, and monkeys. Xenobiotica. 2015 Jan;45(1):60-70.  [Content Brief]

    • [1]. Kobayashi M, et al. In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother. 2011 Feb;55(2):813-21.

      [2]. Hare S, et al. Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol. 2011 Oct;80(4):565-72.

      [3]. Moss L, et al. The comparative disposition and metabolism of dolutegravir, a potent HIV-1 integrase inhibitor, in mice, rats, and monkeys. Xenobiotica. 2015 Jan;45(1):60-70.

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 2.3845 mL 11.9224 mL 23.8447 mL 59.6118 mL
    5 mM 0.4769 mL 2.3845 mL 4.7689 mL 11.9224 mL
    10 mM 0.2384 mL 1.1922 mL 2.3845 mL 5.9612 mL
    15 mM 0.1590 mL 0.7948 mL 1.5896 mL 3.9741 mL
    20 mM 0.1192 mL 0.5961 mL 1.1922 mL 2.9806 mL
    • No file chosen (Maximum size is: 1024 Kb)
    • If you have published this work, please enter the PubMed ID.
    • Your name will appear on the site.

    Dolutegravir Related Classifications

    • Metabolic Enzyme/Protease Anti-infection
    • HIV Integrase HIV
    Help & FAQs

    • Keywords:

      Dolutegravir1051375-16-6S/GSK1349572HIV IntegraseHIVHuman immunodeficiency virusInhibitorinhibitorinhibit

    Vous serez peut-être également intéressé par les produits suivants :



    Référence
    Description
    Cond.
    Prix HT