U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C20H19F2N3O5
Molecular Weight 419.3788
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DOLUTEGRAVIR

SMILES

C[C@@H]1CCO[C@H]2CN3C=C(C(=O)NCC4=C(F)C=C(F)C=C4)C(=O)C(O)=C3C(=O)N12

InChI

InChIKey=RHWKPHLQXYSBKR-BMIGLBTASA-N
InChI=1S/C20H19F2N3O5/c1-10-4-5-30-15-9-24-8-13(17(26)18(27)16(24)20(29)25(10)15)19(28)23-7-11-2-3-12(21)6-14(11)22/h2-3,6,8,10,15,27H,4-5,7,9H2,1H3,(H,23,28)/t10-,15+/m1/s1

HIDE SMILES / InChI

Description

Dolutegravir is an integrase inhibitor that is meant to be used as part of combination therapy for the treatment of HIV. Dolutegravir inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of retroviral deoxyribonucleic acid (DNA) integration which is essential for the HIV replication cycle. Dolutegravir coadministered with dofetilide can result in potentially life-threatening adverse events.

CNS Activity

Originator

Approval Year

Target Info

Target Info

Primary TargetPharmacologyConditionPotency
2.7 nM [IC50]
Condition Info

Condition Info

ConditionModalityTargetsHighest PhaseProduct
Primary
TIVICAY
PMID

PMID

TitleDatePMID
Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers.
2010 Jan
S/GSK1349572, a new integrase inhibitor for the treatment of HIV: promises and challenges.
2011 Apr
Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572).
2011 Oct
Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults.
2011 Sep 10
Dolutegravir for the treatment of HIV.
2012 Apr
The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adults.
2012 Nov 1
Antiretroviral therapy: dolutegravir sets SAIL(ING).
2013 Aug 24
Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study.
2013 Aug 24
In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor.
2013 Feb
Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness.
2013 Jun
Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir.
2013 Nov
Dolutegravir: first global approval.
2013 Sep
Dolutegravir (Tivicay) for HIV.
2013 Sep 30
Patent

Sample Use Guides

In Vivo Use Guide
The recommended dose is 50 mg once daily or twice daily depending on therapy.
Route of Administration: Oral
In Vitro Use Guide
Dolutegravir exhibited antiviral activity against laboratory strains of wild-type HIV-1 with mean EC50 values of 0.5 nM (0.21 ng/mL) to 2.1 nM (0.85 ng/mL) in peripheral blood mononuclear cells (PBMCs) and MT-4 cells. Dolutegravir exhibited antiviral activity against 13 clinically diverse clade B isolates with a mean EC50 value of 0.52 nM in a viral integrase susceptibility assay using the integrase coding region from clinical isolates. Dolutegravir demonstrated antiviral activity in cell culture against a panel of HIV-1 clinical isolates (3 in each group of M clades A, B, C, D, E, F, and G, and 3 in group O) with EC50 values ranging from 0.02 nM to 2.14 nM for HIV-1. Dolutegravir EC50 values against 3 HIV-2 clinical isolates in PBMC assays ranged from 0.09 nM to 0.61 nM.
Name Type Language
DOLUTEGRAVIR
DASH   INN   MI   USAN   VANDF   WHO-DD  
INN   USAN  
Official Name English
S-349572
Code English
DOLUTEGRAVIR [INN]
Common Name English
GSK1349572A
Code English
DTG
Common Name English
DOLUTEGRAVIR [WHO-DD]
Common Name English
DOLUTEGRAVIR [USAN]
Common Name English
GSK1349572
Code English
GSK-1349572
Code English
DOLUTEGRAVIR [VANDF]
Common Name English
DOLUTEGRAVIR [MI]
Common Name English
GSK 1349572
Code English
(4R,12.ALPHA.S)-N-((2,4-DIFLUOROPHENYL)METHYL)-7-HYDROXY-4-METHYL-6,8-DIOXO-3,4,6,8,12,12.ALPHA.-HEXAHYDRO-2H-PYRIDO(1',2':4,5)PYRAZINO(2,1-.BETA.)(1,3)OXAZINE-9-CARBOXAMIDE
Common Name English
Classification Tree Code System Code
WHO-ATC J05AR13
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
WHO-VATC QJ05AX12
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
WHO-ATC J05AX12
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
Code System Code Type Description
NCI_THESAURUS
C121543
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY
HSDB
1051375-16-6
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY
ChEMBL
CHEMBL1229211
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY
DRUG BANK
DB08930
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY
CAS
1051375-16-6
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY
PUBCHEM
54726191
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY SWITZERF
EVMPD
SUB35122
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY
INN
9261
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY
RXCUI
1433868
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY RxNorm
MESH
C562325
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY
MERCK INDEX
M4730
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY Merck Index
NDF-RT
N0000187061
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY Organic Cation Transporter 2 Inhibitors [MoA]
LactMed
1051375-16-6
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY
WIKIPEDIA
DOLUTEGRAVIR
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY
NDF-RT
N0000191423
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY Multidrug and Toxin Extrusion Transporter 1 Inhibitors [MoA]
IUPHAR
7365
Created by admin on Tue Mar 06 11:14:40 UTC 2018 , Edited by admin on Tue Mar 06 11:14:40 UTC 2018
PRIMARY