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: 1051375-16-6

Selleck's Dolutegravir has been cited by 27 Publications

3 Customer Reviews

Purity & Quality Control

Batch: Purity: 99.85%
99.85

Products often used together with Dolutegravir

Bictegravir

Dolutegravir, but not bictegravir represses gene expression and release of adiponectin and leptin in Simpson-Golabi-Behmel syndrome (SGBS) human adipocytes.

Domingo P, et al. Life Sci. 2022 Nov 1;308:120948.

Rilpivirine

Dolutegravir and Rilpivirine are the first dual antiretroviral single tablet combination regimens (STRs) approved by FDA for the maintenance therapy of HIV-1 infection.

Dowers E, et al. HIV AIDS (Auckl). 2018; 10: 215–224.

Lamivudine

Dolutegravir and Lamivudine show lasting effectiveness without increased resistance risk and lower drug-related side effects in adults with HIV-1 infection.

Cahn P, et al. J Acquir Immune Defic Syndr. 2020 Mar 1;83(3):310-318.

Abacavir

Dolutegravir and Abacavir with lamivudine as triple combination therapy is effective and an well tolerated option for the management of HIV-1 infection.

Greig SL, et al. Drugs. 2015 Apr;75(5):503-14.

Atazanavir

Dolutegravir and Atazanavir with Ritonavir is a safe and effective therapy for HIV patients with treatment failure and resistance.

Spagnuolo V, et al. Drug Des Devel Ther. 2019 Jan 24;13:477-479.

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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
Click to View More Cell Line Experimental Data

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
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
NCT05122026 Not yet recruiting HIV Seropositivity|Pregnancy|Tuberculosis Infection The Aurum Institute NPC|Johns Hopkins University|Weill Medical College of Cornell University|University of Washington January 30 2023 Phase 1|Phase 2

Chemical lnformation & 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 : 84 mg/mL ( (200.29 mM)； Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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