DOLUTEGRAVIR

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 Search

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

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204790Orig1s008lbl.pdf

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 Target	Pharmacology	Condition	Potency
Human immunodeficiency virus type 1 integrase 19 Target ID: CHEMBL3471 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204790Orig1s008lbl.pdf	Inhibitor 8297		2.7 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
HIV-1 infection 151 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/204790Orig1s008lbl.pdf	Primary		Approved 8429	TIVICAY Approved Use Indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 30 kg. Launch Date 2013

C_max

Value	Dose	Co-administered	Analyte	Population
3.67 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DOLUTEGRAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.15 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		[NO STEREO] DOLUTEGRAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
53.6 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DOLUTEGRAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
75.1 μg × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		[NO STEREO] DOLUTEGRAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
14 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DOLUTEGRAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		[NO STEREO] DOLUTEGRAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
1.1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf	50 mg 1 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DOLUTEGRAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204790lbl.pdf	50 mg 2 times / day steady-state, oral dose: 50 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		[NO STEREO] DOLUTEGRAVIR plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
50 mg 1 times / day steady, oral Recommended Dose: 50 mg, 1 times / day Route: oral Route: steady Dose: 50 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/30272231	healthy, 33.5 years (range 24–63 years) n = 11 Health Status: healthy Age Group: 33.5 years (range 24–63 years) Sex: M+F Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/30272231	Sources: https://pubmed.ncbi.nlm.nih.gov/30272231
250 mg single, oral Studied dose Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22422361	healthy, 34.5 ± 10.5 years n = 41 Health Status: healthy Age Group: 34.5 ± 10.5 years Sex: M+F Population Size: 41 Sources: https://pubmed.ncbi.nlm.nih.gov/22422361	Other AEs: Nausea, Headache... Other AEs: Nausea (20%) Headache (7%) Abdominal pain (5%) Diarrhea (2%) Dizziness (2%) Oropharyngeal pain (2%) Vomiting (2%) Viral infection (2%) Sources: https://pubmed.ncbi.nlm.nih.gov/22422361

AEs

AE	Significance	Dose	Population
Diarrhea	2%	250 mg single, oral Studied dose Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22422361	healthy, 34.5 ± 10.5 years n = 41 Health Status: healthy Age Group: 34.5 ± 10.5 years Sex: M+F Population Size: 41 Sources: https://pubmed.ncbi.nlm.nih.gov/22422361
Dizziness	2%	250 mg single, oral Studied dose Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22422361	healthy, 34.5 ± 10.5 years n = 41 Health Status: healthy Age Group: 34.5 ± 10.5 years Sex: M+F Population Size: 41 Sources: https://pubmed.ncbi.nlm.nih.gov/22422361
Oropharyngeal pain	2%	250 mg single, oral Studied dose Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22422361	healthy, 34.5 ± 10.5 years n = 41 Health Status: healthy Age Group: 34.5 ± 10.5 years Sex: M+F Population Size: 41 Sources: https://pubmed.ncbi.nlm.nih.gov/22422361
Viral infection	2%	250 mg single, oral Studied dose Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22422361	healthy, 34.5 ± 10.5 years n = 41 Health Status: healthy Age Group: 34.5 ± 10.5 years Sex: M+F Population Size: 41 Sources: https://pubmed.ncbi.nlm.nih.gov/22422361
Vomiting	2%	250 mg single, oral Studied dose Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22422361	healthy, 34.5 ± 10.5 years n = 41 Health Status: healthy Age Group: 34.5 ± 10.5 years Sex: M+F Population Size: 41 Sources: https://pubmed.ncbi.nlm.nih.gov/22422361
Nausea	20%	250 mg single, oral Studied dose Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22422361	healthy, 34.5 ± 10.5 years n = 41 Health Status: healthy Age Group: 34.5 ± 10.5 years Sex: M+F Population Size: 41 Sources: https://pubmed.ncbi.nlm.nih.gov/22422361
Abdominal pain	5%	250 mg single, oral Studied dose Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22422361	healthy, 34.5 ± 10.5 years n = 41 Health Status: healthy Age Group: 34.5 ± 10.5 years Sex: M+F Population Size: 41 Sources: https://pubmed.ncbi.nlm.nih.gov/22422361
Headache	7%	250 mg single, oral Studied dose Dose: 250 mg Route: oral Route: single Dose: 250 mg Sources: https://pubmed.ncbi.nlm.nih.gov/22422361	healthy, 34.5 ± 10.5 years n = 41 Health Status: healthy Age Group: 34.5 ± 10.5 years Sex: M+F Population Size: 41 Sources: https://pubmed.ncbi.nlm.nih.gov/22422361

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:76010	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:76010
ChemicalBook	CB62538916	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB62538916
MolPort	MolPort-023-293-507	https://www.molport.com/shop/molecule-link/MolPort-023-293-507
Selleck Chemicals	s-gsk1349572	http://www.selleckchem.com/products/s-gsk1349572.html
ZINC	ZINC000058581064	http://zinc15.docking.org/substances/ZINC000058581064

PubMed

Title	Date	PubMed
Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers.	2010 Jan	19884365
S/GSK1349572, a new integrase inhibitor for the treatment of HIV: promises and challenges.	2011 Apr	21381981
Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572).	2011 Oct	21719464
Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults.	2011 Sep 10	21716073
Dolutegravir for the treatment of HIV.	2012 Apr	22380682
The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adults.	2012 Nov 1	22878423
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	23132334
Impact of primary elvitegravir resistance-associated mutations in HIV-1 integrase on drug susceptibility and viral replication fitness.	2013 Jun	23529738
Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir.	2013 Nov	23824675
Dolutegravir: first global approval.	2013 Sep	24052331
Dolutegravir (Tivicay) for HIV.	2013 Sep 30	24081387

Patents

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 Created by `admin` on `Fri Dec 15 18:45:28 GMT 2023` Edited by `admin` on `Fri Dec 15 18:45:28 GMT 2023`
Record UNII	DKO1W9H7M1
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DOLUTEGRAVIR

Official Name

English

S-349572

Code

English

dolutegravir [INN]

Common Name

English

GSK1349572A

Code

English

Dolutegravir [WHO-DD]

Common Name

English

DTG

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

NCI_THESAURUS

C281