Dolutegravir

Summary

Dolutegravir (CHEMBL1229211) is an approved small-molecule HIV-1 integrase inhibitor (ATC J05AJ03); indicated across 8 conditions including viral infectious disease and hiv infectious disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: J05AJ03
• Indications: 8 conditions
• Clinical trials: 150
• Chemistry: 419.4 Da · C20H19F2N3O5

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1229211
Name	Dolutegravir
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	54726191
ChEBI	CHEBI:76010
ATC	J05AJ03
Molecular formula	C20H19F2N3O5
Molecular weight	419.4
InChIKey	RHWKPHLQXYSBKR-BMIGLBTASA-N

SMILES: C[C@@H]1CCO[C@@H]2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)O

IUPAC name: (3S,7R)-N-[(2,4-difluorophenyl)methyl]-11-hydroxy-7-methyl-9,12-dioxo-4-oxa-1,8-diazatricyclo[8.4.0.03,8]tetradeca-10,13-diene-13-carboxamide

ChEBI definition: A monocarboxylic acid amide obtained by formal condensation of the carboxy group of (4R,12aS)-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-carboxylic acid with the amino group of 2,4-difluorobenzylamine. Used (as its sodium salt) for treatment of HIV-1.

Pharmacological roles (ChEBI): HIV-1 integrase inhibitor.

Also known as: Dolutegravir, GSK 1349572, GSK-1349572, GSK1349572, GSK1349572A, S-349572, DOLUTEGRAVIR, SID174007466, Dolutegravir (GSK1349572)

Parent form; salt/anhydrous children: CHEMBL1213165

Patent coverage: 1,394 distinct patent families (3,337 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 3,028 (91%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 8 (assay-derived). Sample: Solute carrier family 22 member 2, Vesicular acetylcholine transporter, Cytochrome P450 3A4, Sigma non-opioid intracellular receptor 1, Sigma intracellular receptor 2, Sigma intracellular receptor 2, Sigma non-opioid intracellular receptor 1, Broad substrate specificity ATP-binding cassette transporter ABCG2.

Bioactivity

ChEMBL activities: 9 potent at pChembl ≥ 5 of 13 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
TMEM97	7.75	Ki	18	nM	CHEMBL_ACT_20652145
Q5U3Y7	7.75	Ki	18	nM	CHEMBL_ACT_24796383
Q5U3Y7	7.53	Ki	29.5	nM	CHEMBL_ACT_24415848
Q5U3Y7	7.5	Ki	32	nM	CHEMBL_ACT_18338335
Q60492	7.15	Ki	71	nM	CHEMBL_ACT_15157421
Q60492	6.91	Ki	124	nM	CHEMBL_ACT_24796408
Q9R0C9	6.66	Ki	217	nM	CHEMBL_ACT_18338329
SLC22A2	5.72	IC50	1900	nM	CHEMBL_ACT_15468078
Q62666	5.34	Ki	4523	nM	CHEMBL_ACT_18338341

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

8 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
viral infectious disease	3	MONDO:0005108	EFO:0000763
HIV infectious disease	3	MONDO:0005109	EFO:0000764
AIDS	3	MONDO:0012268	EFO:0000765
malaria	1	MONDO:0005136	EFO:0001068
amyotrophic lateral sclerosis	1	MONDO:0004976	MONDO:0004976

3 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 150.

Phase distribution

Phase	Trials
PHASE1	42
PHASE4	30
PHASE3	27
PHASE2	22
Not specified	21
PHASE1/PHASE2	5
PHASE2/PHASE3	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02656511	PHASE4	ACTIVE_NOT_RECRUITING	Immediate Initiation of Antiretroviral Therapy During Hyperacute HIV Infection
NCT05630638	PHASE4	RECRUITING	Doravirine Dose Optimisation in Pregnancy
NCT06485154	PHASE4	ACTIVE_NOT_RECRUITING	Post-Injectable Cabotegravir Antiretroviral Salvage Strategy Options Trial
NCT06787976	PHASE4	NOT_YET_RECRUITING	Effect of Dolutegravir Compared With Darunavir/Cobicistat on the Severity of Neuropsychiatric Effects al 12 Weeks in Antirretroviral Treatment-Naive Adults.
NCT02098837	PHASE4	COMPLETED	Cardiovascular Risk in HIV Patients Switching From a Boosted Protease Inhibitor (PI) to Dolutegravir (DTG)
NCT02211482	PHASE4	COMPLETED	Dolutegravir-Lamivudine as Dual Therapy in Naive HIV-Infected Patients: A Pilot Study
NCT02337322	PHASE4	UNKNOWN	Immune Recovery in Advanced , ARV-naïve, HIV-1-infected Individuals Taking Dolutegravir or Ritonavir-boosted Darunavir
NCT02401828	PHASE4	COMPLETED	The Dolutegravir Antiretroviral Mono-Therapy for HIV Trial
NCT02487706	PHASE4	COMPLETED	Assessment of Dolutegravir Removed by Hemodialysis in HIV-infected Patients With End-stage Renal Disease
NCT02500446	PHASE4	COMPLETED	Dolutegravir Impact on Residual Replication
NCT02513147	PHASE4	COMPLETED	HIV Reservoir Dynamics After Switching to Dolutegravir in Patients on a PI and 2 NRTI Based Regimen
NCT02519777	PHASE4	COMPLETED	Integrase and Maraviroc Intensification in Neurocognitive Dysfunction (InMIND)
NCT02659761	PHASE4	TERMINATED	Triumeq As an Integrase Single Tablet Regimen in People With HIV Who Inject Drugs
NCT02924389	PHASE4	TERMINATED	Dolutegravir in Reservoirs
NCT03017872	PHASE4	UNKNOWN	Dolutegravir and Darunavir Evaluation in Adults Failing Therapy
NCT03218592	PHASE4	COMPLETED	ENLIGHTEN: Establishing Novel Antiretroviral (ARV) Imaging for Hair to Elucidate Non-Adherence
NCT03314064	PHASE4	COMPLETED	Phase 4 Study of Dolutegravir (DTG) in Russian Federation
NCT03360682	PHASE4	COMPLETED	Clinical Trial to Evaluate the Efficacy, Pharmacokinetics (PK) Interactions and Safety of Dolutegravir Plus 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in HIV-1-Infected Solid Organ Transplant Patients
NCT03813979	PHASE4	WITHDRAWN	Pharmacokinetics of Single-dose Dolutegravir in HIV-seronegative Subjects With Severe Hepatic Impairment Compared to Matched Controls.
NCT04166474	PHASE4	COMPLETED	Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin
NCT04183738	PHASE4	WITHDRAWN	Inflammation and Co-Infections in D²EFT
NCT04225325	PHASE4	UNKNOWN	Implication for Strategies of Long Term Control of Viral Replication in Patient With Primary HIV Infection (PHI).
NCT04229290	PHASE4	COMPLETED	Second-line Switch to Dolutegravir Study
NCT04340388	PHASE4	COMPLETED	Contribution of Dolutegravir to Obesity and Cardiovascular Disease
NCT04585737	PHASE4	COMPLETED	Efficacy of Switching to DTG/3TC in Virologically-suppressed Adults Currently on B/F/TAF
NCT04746547	PHASE4	UNKNOWN	Pharmacokinetics of Twice or Once Daily DTG (50mg) in Children With HIV and TB
NCT04826562	PHASE4	UNKNOWN	Switch to DOVATO in Patients Suppressed on Biktarvy (SOUND)
NCT04884139	PHASE4	COMPLETED	DTG/3TC vs. BIC/FTC/TAF Maintenance Therapy in People Living With HIV:
NCT04904406	PHASE4	COMPLETED	Changes in Weight, Body Composition and Cardiac Risk After Discontinuing Abacavir Treatment in HIV-infected Individuals
NCT04910711	PHASE4	UNKNOWN	Investigating the Interaction Between Two Long-acting Reversible Methods of Contraception and Dolutegravir, a Treatment for HIV
NCT04892654	PHASE3	RECRUITING	Efficacy of Doravirine + Dolutegravir Dual Therapy in the Context of Antiretroviral Therapy Switch
NCT05979311	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of Using an Oral Once-daily 2 Drug Regimen Compared to an Oral Once-daily 3 Drug Regimen for the Treatment of Human Immunodeficiency Virus (HIV)-1 in Adults Who Have Not Previously Taken Antiretroviral Therapy
NCT06203132	PHASE3	RECRUITING	DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection
NCT06747507	PHASE3	RECRUITING	Ndovu RCT: Investing the Optimal Management of Dolutegravir Resistance
NCT01227824	PHASE3	COMPLETED	A Trial Comparing GSK1349572 50mg Once Daily to Raltegravir 400mg Twice Daily
NCT01231516	PHASE3	COMPLETED	A Study of GSK1349572 Versus Raltegravir (RAL) With Investigator Selected Background Regimen in Antiretroviral-Experienced, Integrase Inhibitor-Naive Adults
NCT01263015	PHASE3	COMPLETED	A Trial Comparing GSK1349572 50mg Plus Abacavir/Lamivudine Once Daily to Atripla (Also Called The SINGLE Trial)
NCT01328041	PHASE3	COMPLETED	A Study to Assess Dolutegravir in HIV-infected Subjects With Treatment Failure on an Integrase Inhibitor Containing Regimen.
NCT01499199	PHASE3	COMPLETED	A Study of the Pharmacokinetics and Antiviral Activity of Dolutegravir in the Central Nervous System in HIV-1 Infected ART-naive Subjects
NCT01837277	PHASE2/PHASE3	COMPLETED	Impact of a Dolutegravir-based Regimen on Early Mortality of AIDS Patients

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 2 clinical and 24 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).