Home Microbiology Integrase inhibitor Dolutegravir For research use only.

Dolutegravir

Synonyms: GSK1349572,S/GSK1349572

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.

Dolutegravir Chemical Structure

Dolutegravir Chemical Structure

CAS No. 1051375-16-6

Purity & Quality Control

Dolutegravir Related Products

Signaling Pathway

Integrase Signaling Pathways

Integrase Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MDCK2 cells Function assay Inhibition of human OCT2 expressed in MDCK2 cells using [14C]metformin as substrate by liquid scintillation counting analysis 23132334
HOS Antiviral assay 3 hrs 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, EC50 = 0.0016 μM. 24901667
HEK293T Antiviral assay 2 days Antiviral activity against pseudo Human immunodeficiency virus infected in HEK293T cells after 2 days, IC50 = 0.0017 μM. 23845180
MT4 Antiviral assay 4 to 5 days Antiviral activity against Human immunodeficiency virus 1 3B infected in human MT4 cells after 4 to 5 days by bioluminescence assay, IC50 = 0.002 μM. 23845180
HOS Antiviral assay 3 hrs 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, EC50 = 0.0036 μM. 24901667
HOS Antiviral assay 3 hrs 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, EC50 = 0.0043 μM. 24901667
HOS Antiviral assay 3 hrs 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, EC50 = 0.0058 μM. 24901667
HOS Antiviral assay 3 hrs 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, EC50 = 0.011 μM. 24901667
HOS Antiviral assay 3 hrs 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, EC50 = 0.013 μM. 24901667
P4R5 MAGI Antiviral assay 24 hrs Antiviral activity against HIV1 infected in CD4/CXCR4/CCR5 expressing human P4R5 MAGI cells preincubated with cells for 24 hrs followed by viral infection measured after 48 hrs by beta-galactosidase reporter gene assay, EC50 = 0.02 μM. 30031976
P4R5 Antiviral assay 24 hrs Antiviral activity against HIV1 infected in CD4/CXCR4/CCR5 expressing human P4R5 cells assessed as inhibition of viral replication preincubated with cells for 24 hrs followed by viral infection measured after 48 hrs by beta-galactosidase reporter gene ass, EC50 = 0.02 μM. 28525279
HEK293T Antiviral assay 2 days Antiviral activity against pseudo Human immunodeficiency virus infected in HEK293T cells after 2 days in presence of human serum albumin, IC50 = 0.022 μM. 23845180
MDCK2 Function assay Inhibition of human OCT2 expressed in MDCK2 cells using [14C]metformin as substrate by liquid scintillation counting analysis, IC50 = 1.9 μM. 23132334
Vero E6 Antiviral assay 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, EC50 = 22.04 μM. ChEMBL
Vero E6 Antiviral assay 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, EC90 = 42.81 μM. ChEMBL
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Biological Activity

Description 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.
Features A next-generation and two-metal-binding HIV integrase strand transfer inhibitor.
Targets
HIV integrase [2]
(Cell-free assay)
2.7 nM
In vitro
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]
Kinase Assay In vitro strand transfer assay
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.
Cell Research Cell lines MT-4
Concentrations 0 to 10 μM
Incubation Time 4 days or 5 days
Method

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].
Experimental Result Images Methods Biomarkers Images PMID
Dose-response infectivity curves NL4.3IN(WT) / NL4.3IN(S230R) virus 29617824
In Vivo
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.
Animal Research Animal Models C3H/HeJ mice
Dosages 50 mg/kg
Administration o.g.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT06281834 Not yet recruiting
Pediatric HIV Infection|Latent Tuberculosis
Brigham and Women''s Hospital|APIN Public Health Initiatives|University of Cape Town
 May 2024 Phase 1
NCT05122026 Recruiting
HIV Seropositivity|Pregnancy|Tuberculosis Infection
The Aurum Institute NPC|Johns Hopkins University|Weill Medical College of Cornell University|University of Washington
 January 17 2024 Phase 1|Phase 2
NCT05069688 Recruiting
Pediatric HIV Infection|Tuberculosis Infection
Brigham and Women''s Hospital|APIN Public Health Initiatives|University of Cape Town
 July 7 2023 Phase 1
NCT05122767 Recruiting
Tuberculosis|HIV
The Aurum Institute NPC|Johns Hopkins University
 May 24 2023 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 419.38 Formula

C20H19F2N3O5
CAS No. 1051375-16-6 SDF Download Dolutegravir SDF
Smiles CC1CCOC2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)O
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 83 mg/mL ( (197.91 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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