1. Anti-infection
    Metabolic Enzyme/Protease
  2. HIV Integrase
    HIV

Dolutegravir (Synonyms: S/GSK1349572; GSK1349572; S/GSK 1349572; GSK-1349572; GSK 1349572)

Cat. No.: HY-13238 Purity: 99.54%
Handling Instructions

Dolutegravir is an inhibitor of HIV-1 integrase-catalyzed strand transfer with IC50 of 2.7 nM.

For research use only. We do not sell to patients.
Dolutegravir Chemical Structure

Dolutegravir Chemical Structure

CAS No. : 1051375-16-6

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10 mM * 1 mL in DMSO $182 In-stock
5 mg $165 In-stock
10 mg $230 In-stock
50 mg $585 In-stock
100 mg $1064 In-stock
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Description

Dolutegravir is an inhibitor of HIV-1 integrase-catalyzed strand transfer with IC50 of 2.7 nM.

IC50 & Target

IC50: 2.7 nM (HIV-1 integrase)[1]

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].

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[2].

Clinical Trial
Sponsor Condition Start Date Phase
ViiV Healthcare HIV-1 infection 2013-08-31 Phase 3
ViiV Healthcare HIV-1 infection 2012-01-31 Phase 3
ViiV Healthcare HIV-1 infection 2011-10-31 Phase 3
Fundacio Lluita Contra La Sida HIV-1 infection 2013-09-03 Phase 3
ViiV Healthcare HIV-1 infection 2012-04-30 Phase 3
References
Preparing Stock Solutions
Concentration Volume (DMSO) 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
Cell Assay
[1]

Dolutegravir (S/GSK1349572) is dissolved in stock solutions, and then diluted with appropriate media before use[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].

Animal Administration
[2]

Dolutegravir (S/GSK1349572) is formulated as a solution in N,N-dimethylacetamide and diluted with 50 mM N-methylglucamine in 3% mannitol (intravenous)[2].
Dolutegravir (S/GSK1349572) is formulated as a solution in D:Solutol:50 mM N-methylglucamine in 3% mannitol (1:1:8, v:w:v) (orally administered to fasted rats and monkeys)[2].
Dolutegravir (S/GSK1349572) is formulated as a suspension in 0.5% hydroxypropyl methylcellulose (HPMC)/0.1% polyoxyethylene sorbitan monooleate (Tween 80) (orally administered to non-fasted rats and monkeys)[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.

References
M.Wt

419.38

Formula

C₂₀H₁₉F₂N₃O₅

CAS No.

1051375-16-6

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: 10 mg/mL

Purity: 99.54%

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Dolutegravir
Cat. No.:
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