| Drug General Information |
|---|
| Drug ID |
D00YZD |
| Drug Name |
Dolutegravir |
Drug Info
|
| Synonyms |
S/GSK1349572; DTG |
| 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 |
[555922],
[556030]
|
| Level of Resistance |
Reduce DTG susceptibility 6 fold |
|
|
|
|
|
|
|
|
|
| Mutation info |
Missense: G118R |
[556227],
[556228]
|
| Level of Resistance |
Low-level resistance |
|
|
|
|
|
|
|
|
|
| Mutation info |
Missense: Q148H |
[556227],
[556228]
|
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: Q148K |
[556227],
[556228]
|
| Level of Resistance |
Intermediate resistance |
|
| Mutation info |
Missense: Q148R |
[556227],
[556228]
|
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: S153F |
[556227],
[556228]
|
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: T66K |
[556227],
[556228]
|
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: V151L |
[556227],
[556228]
|
| Level of Resistance |
Low-level resistance |
|
| Mutation info |
Missense: S153Y |
[555782]
|
| Level of Resistance |
Reduce DTG susceptibility about 2 fold |
|
| References |
|---|
| Ref 532651 | 2013 FDA drug approvals. Nat Rev Drug Discov. 2014 Feb;13(2):85-9. |
|---|
| Ref 542387 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7365). |
|---|
| Ref 556227 | HIV drug development: the next 25 years. Nat Rev Drug Discov. 2007 Dec;6(12):959-66. |
|---|
| Ref 555782 | In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother. 2011 Feb;55(2):813-21. doi: 10.1128/AAC.01209-10. Epub 2010 Nov 29. |
|---|
| Ref 556228 | The HIVdb system for HIV-1 genotypic resistance interpretation. Intervirology. 2012;55(2):98-101. doi: 10.1159/000331998. Epub 2012 Jan 24. |
|---|
| Ref 555922 | Viral fitness cost prevents HIV-1 from evading dolutegravir drug pressure. Retrovirology. 2013 Feb 22;10:22. doi: 10.1186/1742-4690-10-22. |
|---|
| Ref 556030 | 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. doi: 10.1093/jac/dku387. Epub 2014 Oct 3. |
|---|
