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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

[H][C@]12CN3C=C(C(=O)NCC4=CC=C(F)C=C4F)C(=O)C(O)=C3C(=O)N1[C@H](C)CCO2

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

Molecular Formula C20H19F2N3O5
Molecular Weight 419.3788
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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

Targets

Primary TargetPharmacologyConditionPotency
2.7 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
TIVICAY

Cmax

ValueDoseCo-administeredAnalytePopulation
3.67 μg/mL
50 mg 1 times / day steady-state, oral
DOLUTEGRAVIR plasma
Homo sapiens
4.15 μg/mL
50 mg 2 times / day steady-state, oral
[NO STEREO] DOLUTEGRAVIR plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
53.6 μg × h/mL
50 mg 1 times / day steady-state, oral
DOLUTEGRAVIR plasma
Homo sapiens
75.1 μg × h/mL
50 mg 2 times / day steady-state, oral
[NO STEREO] DOLUTEGRAVIR plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
14 h
50 mg 1 times / day steady-state, oral
DOLUTEGRAVIR plasma
Homo sapiens
14 h
50 mg 2 times / day steady-state, oral
[NO STEREO] DOLUTEGRAVIR plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
1.1%
50 mg 1 times / day steady-state, oral
DOLUTEGRAVIR plasma
Homo sapiens
1.1%
50 mg 2 times / day steady-state, oral
[NO STEREO] DOLUTEGRAVIR plasma
Homo sapiens

Doses

AEs

PubMed

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.
Substance Class Chemical
Record UNII
DKO1W9H7M1
Record Status Validated (UNII)
Record Version