Reagenzien und Instrumente für die Immunologie Zellbiologie und Molekularbiologie

Dolutegravir [1051375-16-6]

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Katalog-Nummer HY-13238-10mg

Size : 10mg

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Telefonnummer : +1 850 650 7790

Marke : MedChemExpress

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Contact local distributor :

Telefonnummer : +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).

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Dolutegravir Chemische Struktur

CAS. Nr. : 1051375-16-6

Größe	Verfügbarkeit	Menge
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	Auf Lager	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	Auf Lager	Estimated Time of Arrival: December 31
Solid
2 mg	Auf Lager	Estimated Time of Arrival: December 31
5 mg	Auf Lager	Estimated Time of Arrival: December 31
10 mg	Auf Lager	Estimated Time of Arrival: December 31
50 mg	Auf Lager	Estimated Time of Arrival: December 31
100 mg	Auf Lager	Estimated Time of Arrival: December 31
200 mg	Auf Lager	Estimated Time of Arrival: December 31
500 mg	Auf Lager	Estimated Time of Arrival: December 31
1 g	Auf Lager	Estimated Time of Arrival: December 31
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Based on 26 publication(s) in Google Scholar

Other Forms of Dolutegravir:

Cabotegravir In-stock
Dolutegravir sodium In-stock
Dolutegravir-d6 Angebot einholen
Dolutegravir-d₃ Angebot einholen
Dolutegravir-d₅ Angebot einholen
Dolutegravir (Standard) Angebot einholen

: 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).

Beschreibung

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.

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 (V_SS) 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 (C_max 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.

Klinische Studie

Molekulargewicht

419.38

Formel

C₂₀H₁₉F₂N₃O₅

CAS. Nr.

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@@](19)(N4C3=O)OCC[C@H]4C)=O

Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Lösungsmittel & Löslichkeit

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
10 mM	0.2384 mL	1.1922 mL	2.3845 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.

Molaritätsrechner
Verdünnungsrechner

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

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

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

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.
Protocol 3

Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in 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 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Protocol 4

Add each solvent one by one: 10% DMSO 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.96 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

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.

Reinheit & Dokumentation

Purity: 99.98%

Select Batch:

SDS (398 KB)

COA (248 KB) LCMS (93 KB)

Handling Instructions (2659 KB)

Verweise

[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]

Zellassay ^[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 hat die Genauigkeit dieser Methoden nicht unabhängig bestätigt. Sie dienen nur als Referenz.
Tierverwaltung ^[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 hat die Genauigkeit dieser Methoden nicht unabhängig bestätigt. Sie dienen nur als Referenz.
Verweise	[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]

Complete Stock Solution Preparation Table

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

Dolutegravir Related Classifications

Metabolic Enzyme/Protease Anti-infection
HIV Integrase HIV

Help & FAQs

Keywords:

Dolutegravir1051375-16-6S/GSK1349572HIV IntegraseHIVHuman immunodeficiency virusInhibitorinhibitorinhibit

Dolutegravir [1051375-16-6]

Katalog-Nummer HY-13238-10mg

Contact local distributor :

Marke : MedChemExpress

Contact local distributor :

Other Forms of Dolutegravir:

Dolutegravir Related Antibodies

Molaritätsrechner

Verdünnungsrechner

Complete Stock Solution Preparation Table

Dolutegravir Related Classifications

Keywords:

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