| Drug General Information |
| Drug ID |
D00YZD
|
| Drug Name |
Dolutegravir |
|
| Synonyms |
1051375-16-6; GSK1349572; Tivicay; S/GSK1349572; Dolutegravir (GSK1349572); S-349572; GSK-1349572; GSK 1349572; UNII-DKO1W9H7M1; (4r,12as)-N-(2,4-Difluorobenzyl)-7-Hydroxy-4-Methyl-6,8-Dioxo-3,4,6,8,12,12a-Hexahydro-2h-Pyrido[1',2':4,5]pyrazino[2,1-B][1,3]oxazine-9-Carboxamide; CHEBI:76010; DKO1W9H7M1; Tivicay (TN); (4R,12aS)-N-[(2,4-Difluorophenyl)methyl]-3,4,6,8,12,12a-hexahydro-7-hydroxy-4-methyl-6,8-dioxo-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide; Dolutegravir Sodium ( |
| Drug Type |
Small molecular drug |
| Company |
GlaxoSmithKline |
| Structure |
|
| Drug Resistance Mutations |
| Target Name |
HIV Integrase |
Target Info |
| Uniprot ID |
POL_HV1B1(1160-1447) |
| Species |
Human immunodeficiency virus type 1 (HIV-1) |
| Reference Sequence |
FLDGIDKAQDEHEKYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQVDCSPGI
WQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVKTIHTDNGSN
FTSATVKAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLKTAVQMAV
FIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQNFRVYYRDSRNPLWKGPAK
LLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVASRQDED [Human immu
nodeficiency virus type 1 (HIV-1)]
|
| Targeted Disease |
HIV infection |
| Drug Resistance Mutations |
| Mutation info |
Missense: R263K |
[1], [2] |
| Level of Resistance |
Reduce DTG susceptibility 6 fold |
|
| Mutation info |
Missense: E138A |
[3], [4] |
|
| Mutation info |
Missense: E138K |
[3], [4] |
|
| Mutation info |
Missense: E138T |
[3], [4] |
|
| Mutation info |
Missense: E92Q |
[3], [4] |
|
| Mutation info |
Missense: G118R |
[3], [4] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: G140A |
[3], [4] |
|
| Mutation info |
Missense: G140C |
[3], [4] |
|
| Mutation info |
Missense: G140S |
[3], [4] |
|
| Mutation info |
Missense: N155H |
[3], [4] |
|
| Mutation info |
Missense: Q148H |
[3], [4] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: Q148K |
[3], [4] |
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: Q148R |
[3], [4] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: S153F |
[3], [4] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: T66K |
[3], [4] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: V151L |
[3], [4] |
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: S153Y |
[5] |
| Level of Resistance |
Reduce DTG susceptibility about 2 fold |
|
| References |
| REF 1 |
Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Retrovirology. 2013 Feb 22;10:22.
|
| REF 2 |
Evolution of a novel pathway leading to dolutegravir resistance in a patient harbouring N155H and multiclass drug resistance. J Antimicrob Chemother. 2015 Feb;70(2):405-11.
|
| REF 3 |
HIV drug development: the next 25 years. Nat Rev Drug Discov. 2007 Dec;6(12):959-66.
|
| REF 4 |
The HIVdb system for HIV-1 genotypic resistance interpretation. Intervirology. 2012;55(2):98-101.
|
| REF 5 |
In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother. 2011 Feb;55(2):813-21.
|
