Identification

Name
Dolutegravir
Accession Number
DB08930
Type
Small Molecule
Groups
Approved
Description

Dolutegravir is indicated for HIV-1 infection for adults and children and adolescents ≥12 years of age and weighing ≥40 kg. It is marketed as Tivicay as dolutegravir sodium. 52.6 mg of dolutegravir sodium is equivalent to 50 mg dolutegravir free acid. FDA approved on August 12, 2013.

Structure
Thumb
Synonyms
Not Available
External IDs
GSK572 / S-349572 / S/GSK1349572
Product Ingredients
IngredientUNIICASInChI Key
Dolutegravir Sodium1Q1V9V5WYQ1051375-19-9UGWJRRXTMKRYNK-VSLILLSYSA-M
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TivicayTablet50 mgOralViiV Healthcare ULC2013-11-08Not applicableCanada
TivicayTablet25 mgOralViiV Healthcare ULC2017-06-20Not applicableCanada
TivicayTablet, film coated50 mg/1OralViiV Healthcare ULC2013-08-13Not applicableUs49702 0228 13 nlmimage10 d23d694b
TivicayTablet, film coated50 mg/1OralA S Medication Solutions2013-08-132017-06-20Us
TivicayTablet, film coated50 mgOralViiV Healthcare ULC2014-01-16Not applicableEu
TivicayTablet, film coated50 mg/1OralRemedy Repack2016-07-11Not applicableUs
TivicayTablet, film coated10 mg/1OralViiV Healthcare ULC2016-06-09Not applicableUs
TivicayTablet10 mgOralViiV Healthcare ULC2017-06-20Not applicableCanada
TivicayTablet, film coated50 mgOralViiV Healthcare ULC2014-01-16Not applicableEu
TivicayTablet, film coated25 mg/1OralViiV Healthcare ULC2016-06-09Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
TriumeqDolutegravir (50 mg) + Abacavir (600 mg) + Lamivudine (300 mg)TabletOralViiV Healthcare ULC2014-10-22Not applicableCanada
TriumeqDolutegravir Sodium (50 mg/1) + Abacavir Sulfate (600 mg/1) + Lamivudine (300 mg/1)Tablet, film coatedOralViiV Healthcare ULC2014-08-22Not applicableUs
TriumeqDolutegravir Sodium (50 mg/1) + Abacavir Sulfate (600 mg/1) + Lamivudine (300 mg/1)Tablet, film coatedOralA S Medication Solutions2014-08-222017-06-20Us
TriumeqDolutegravir Sodium (50 mg/1) + Abacavir Sulfate (600 mg/1) + Lamivudine (300 mg/1)Tablet, film coatedOralA S Medication Solutions2014-08-222017-06-20Us
Categories
UNII
DKO1W9H7M1
CAS number
1051375-16-6
Weight
Average: 419.3788
Monoisotopic: 419.129277143
Chemical Formula
C20H19F2N3O5
InChI Key
RHWKPHLQXYSBKR-BMIGLBTASA-N
InChI
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
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
SMILES
[H][[email protected]]12CN3C=C(C(=O)NCC4=CC=C(F)C=C4F)C(=O)C(O)=C3C(=O)N1[[email protected]](C)CCO2

Pharmacology

Indication

Dolutegravir is indicated in combination with other antiretroviral agents for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and children aged 12 years and older and weighing at least 40 kg.

Structured Indications
Pharmacodynamics

HIV-1 infected subjects on dolutegravir monotherapy demonstrated rapid and dose-dependent antiviral activity with mean declines from baseline to Day 11 in HIV-1 RNA of 1.5, 2.0, and 2.5 log10 for dolutegravir 2 mg, 10 mg, and 50 mg once daily, respectively. Antiviral response was maintained for 3 to 4 days after the last 50 mg dose. Dolutegravir did not prolong the QTc interval over 24 hours postdose. The maximum mean QTc change based on Fridericia correction method (QTcF) for dolutegravir was 2.4 msec (1-sided 95% upper CI: 4.9 msec). Those given a 50 mg once daily dose of dolutegravir also experienced a decrease in creatinine clearance as determined by 24-hour urine collection after 14 days. There is no significant effect on actual glomerular filtration rate or renal plasma flow compared to placebo.

Mechanism of action

Dolutegravir is an HIV-1 antiviral agent. It inhibits HIV integrase by binding to the active site and blocking the strand transfer step to retroviral DNA integration. This is an essential step of the HIV replication cycle and will result in an inhibition of viral activity. Dolutegravir has a mean EC50 value 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.

TargetActionsOrganism
AIntegrase
inhibitor
Human immunodeficiency virus 1
Absorption

When 50 mg of dolutegravir once daily was orally administered to HIV-1 infected adults, the AUC (0-24), Cmax, and Cmin is 53.6 mcg.h/mL, 3.67 mcg/mL, and 1.11 mcg/mL, respectively. The peak plasma concentration was observed 2 to 3 hours post dose. Steady state is achieved within approximately 5 days with average accumulation ratios for AUC, Cmax, and C24h ranging from 1.2 to 1.5. When 50 mg once daily is given to pediatric patients (12 to <18 years and weighing ≥40 kg) the Cmax, AUC (0-24), and C24 is 3.49 mcg/mL, 46 mcg.h/mL, and 0.90 mcg/mL respectively.

Volume of distribution

Volume of distribution (Vd/F), 50 mg once daily = 17.4 L. The median dolutegravir concentration in the CSF was 18 ng/mL after 2 weeks of treatment.

Protein binding

Dolutegravir is highly protein bound (≥98.9%) to human plasma proteins.

Metabolism

Dolutegravir is primarily metabolized by UGT1A1 with some minor contributed CYP3A.

Route of elimination

When a single oral dose of dolutegravir is given, 53% was excreted unchanged in the feces. 31% is excreted in urine in which consists of the ether glucuronide of dolutegravir (18.9%), a metabolite formed by oxidation at the benzylic carbon (3.0%), and its hydrolytic N-dealkylation product (3.6%). Renal elimination of unchanged drug was low (<1%).

Half life

Terminal half life = 14 hours

Clearance

Apparent clearance (CL/F) = 1.0 L/h

Toxicity

The most common adverse reactions of moderate to severe intensity and incidence ≥2% (in those receiving TIVICAY in any one adult trial) are insomnia and headache.

Affected organisms
  • Human Immunodeficiency Virus
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
UDP-glucuronosyltransferase 1-1UGT1A1*28 or UGT1A 7/7Not Availableextra TA in promoterEffect Directly StudiedPoor drug metabolizer.Details
UDP-glucuronosyltransferase 1-1UGT1A1*6Not AvailableG > AEffect Directly StudiedThe presence of this polymorphism in UGT1A1 is associated with reduction in dolutegravir metabolism.Details
UDP-glucuronosyltransferase 1-1UGT1A1*37Not AvailableTA pair insertionEffect Directly StudiedThe presence of this polymorphism in UGT1A1 is associated with reduction in dolutegravir metabolism.Details

Interactions

Drug Interactions
DrugInteractionDrug group
Aluminum hydroxideThe serum concentration of Dolutegravir can be decreased when it is combined with Aluminum hydroxide.Approved
Calcium AcetateThe serum concentration of Dolutegravir can be decreased when it is combined with Calcium Acetate.Approved
Calcium CarbonateThe serum concentration of Dolutegravir can be decreased when it is combined with Calcium Carbonate.Approved
Calcium ChlorideThe serum concentration of Dolutegravir can be decreased when it is combined with Calcium Chloride.Approved
Calcium CitrateThe serum concentration of Dolutegravir can be decreased when it is combined with Calcium Citrate.Approved
Calcium glubionateThe serum concentration of Dolutegravir can be decreased when it is combined with Calcium glubionate.Approved
Calcium GluceptateThe serum concentration of Dolutegravir can be decreased when it is combined with Calcium Gluceptate.Approved
Calcium gluconateThe serum concentration of Dolutegravir can be decreased when it is combined with Calcium gluconate.Approved, Vet Approved
Calcium lactateThe serum concentration of Dolutegravir can be decreased when it is combined with Calcium lactate.Approved, Experimental, Investigational, Vet Approved
Calcium lactate gluconateThe serum concentration of Dolutegravir can be decreased when it is combined with Calcium lactate gluconate.Experimental
Calcium laevulateThe serum concentration of Dolutegravir can be decreased when it is combined with Calcium laevulate.Experimental
Calcium pangamateThe serum concentration of Dolutegravir can be decreased when it is combined with Calcium pangamate.Experimental
Calcium PhosphateThe serum concentration of Dolutegravir can be decreased when it is combined with Calcium Phosphate.Approved
CarbamazepineThe serum concentration of Dolutegravir can be decreased when it is combined with Carbamazepine.Approved, Investigational
CaseinThe serum concentration of Dolutegravir can be decreased when it is combined with Casein.Approved
DofetilideThe serum concentration of Dofetilide can be increased when it is combined with Dolutegravir.Approved
EfavirenzThe serum concentration of Dolutegravir can be decreased when it is combined with Efavirenz.Approved, Investigational
EtravirineThe serum concentration of Dolutegravir can be decreased when it is combined with Etravirine.Approved
Ferric CarboxymaltoseThe serum concentration of Dolutegravir can be decreased when it is combined with Ferric Carboxymaltose.Approved
Ferric CitrateThe serum concentration of Dolutegravir can be decreased when it is combined with Ferric Citrate.Approved, Investigational
Ferric pyrophosphateThe serum concentration of Dolutegravir can be decreased when it is combined with Ferric pyrophosphate.Approved
FosamprenavirThe serum concentration of Dolutegravir can be decreased when it is combined with Fosamprenavir.Approved
FosphenytoinThe serum concentration of Dolutegravir can be decreased when it is combined with Fosphenytoin.Approved
IronThe serum concentration of Dolutegravir can be decreased when it is combined with Iron.Approved
Iron DextranThe serum concentration of Dolutegravir can be decreased when it is combined with Iron Dextran.Approved, Vet Approved
Iron saccharateThe serum concentration of Dolutegravir can be decreased when it is combined with Iron saccharate.Approved
Magnesium HydroxideThe serum concentration of Dolutegravir can be decreased when it is combined with Magnesium Hydroxide.Approved
Magnesium oxideThe serum concentration of Dolutegravir can be decreased when it is combined with Magnesium oxide.Approved
Magnesium salicylateThe serum concentration of Dolutegravir can be decreased when it is combined with Magnesium salicylate.Approved
Magnesium SulfateThe serum concentration of Dolutegravir can be decreased when it is combined with Magnesium Sulfate.Approved, Vet Approved
MetforminThe serum concentration of Metformin can be increased when it is combined with Dolutegravir.Approved
NevirapineThe serum concentration of Dolutegravir can be decreased when it is combined with Nevirapine.Approved
OxcarbazepineThe serum concentration of Dolutegravir can be decreased when it is combined with Oxcarbazepine.Approved
PhenobarbitalThe serum concentration of Dolutegravir can be decreased when it is combined with Phenobarbital.Approved
PhenytoinThe serum concentration of Dolutegravir can be decreased when it is combined with Phenytoin.Approved, Vet Approved
PrimidoneThe serum concentration of Dolutegravir can be decreased when it is combined with Primidone.Approved, Vet Approved
RifampicinThe serum concentration of Dolutegravir can be decreased when it is combined with Rifampicin.Approved
SeleniumThe serum concentration of Dolutegravir can be decreased when it is combined with Selenium.Approved, Vet Approved
St. John's WortThe serum concentration of Dolutegravir can be decreased when it is combined with St. John&#39;s Wort.Investigational, Nutraceutical
SucralfateThe serum concentration of Dolutegravir can be decreased when it is combined with Sucralfate.Approved
TipranavirThe serum concentration of Dolutegravir can be decreased when it is combined with Tipranavir.Approved, Investigational
Food Interactions
Not Available

References

General References
  1. Min S, Song I, Borland J, Chen S, Lou Y, Fujiwara T, Piscitelli SC: Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. Antimicrob Agents Chemother. 2010 Jan;54(1):254-8. doi: 10.1128/AAC.00842-09. Epub 2009 Nov 2. [PubMed:19884365]
  2. Lenz JC, Rockstroh JK: S/GSK1349572, a new integrase inhibitor for the treatment of HIV: promises and challenges. Expert Opin Investig Drugs. 2011 Apr;20(4):537-48. doi: 10.1517/13543784.2011.562189. Epub 2011 Mar 8. [PubMed:21381981]
  3. Min S, Sloan L, DeJesus E, Hawkins T, McCurdy L, Song I, Stroder R, Chen S, Underwood M, Fujiwara T, Piscitelli S, Lalezari J: Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults. AIDS. 2011 Sep 10;25(14):1737-45. doi: 10.1097/QAD.0b013e32834a1dd9. [PubMed:21716073]
  4. Hare S, Smith SJ, Metifiot M, Jaxa-Chamiec A, Pommier Y, Hughes SH, Cherepanov P: Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol. 2011 Oct;80(4):565-72. doi: 10.1124/mol.111.073189. Epub 2011 Jun 30. [PubMed:21719464]
  5. Katlama C, Murphy R: Dolutegravir for the treatment of HIV. Expert Opin Investig Drugs. 2012 Apr;21(4):523-30. doi: 10.1517/13543784.2012.661713. Epub 2012 Mar 2. [PubMed:22380682]
  6. Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF, Richmond G, Buendia CB, Fourie J, Ramgopal M, Hagins D, Felizarta F, Madruga J, Reuter T, Newman T, Small CB, Lombaard J, Grinsztejn B, Dorey D, Underwood M, Griffith S, Min S: Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013 Aug 24;382(9893):700-8. doi: 10.1016/S0140-6736(13)61221-0. Epub 2013 Jul 3. [PubMed:23830355]
  7. Authors unspecified: Dolutegravir (Tivicay) for HIV. Med Lett Drugs Ther. 2013 Sep 30;55(1426):77-9. [PubMed:24081387]
  8. Cottrell ML, Hadzic T, Kashuba AD: Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir. Clin Pharmacokinet. 2013 Nov;52(11):981-94. doi: 10.1007/s40262-013-0093-2. [PubMed:23824675]
  9. Ballantyne AD, Perry CM: Dolutegravir: first global approval. Drugs. 2013 Sep;73(14):1627-37. doi: 10.1007/s40265-013-0121-4. [PubMed:24052331]
  10. Boyd MA, Donovan B: Antiretroviral therapy: dolutegravir sets SAIL(ING). Lancet. 2013 Aug 24;382(9893):664-6. doi: 10.1016/S0140-6736(13)61456-7. Epub 2013 Jul 3. [PubMed:23830358]
External Links
KEGG Drug
D10066
PubChem Compound
54726191
PubChem Substance
175427161
ChemSpider
25051637
ChEBI
76010
ChEMBL
CHEMBL1229211
PharmGKB
PA166114961
HET
DLU
Drugs.com
Drugs.com Drug Page
Wikipedia
Dolutegravir
ATC Codes
J05AR13 — Lamivudine, abacavir and dolutegravirJ05AX12 — Dolutegravir
AHFS Codes
  • 08:18.08.92 — Miscellaneous Antiretrovirals*
PDB Entries
3s3m / 3s3n / 3s3o
FDA label
Download (332 KB)
MSDS
Download (61.6 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
1CompletedNot AvailableHIV-infection/Aids1
1CompletedNot AvailableHealthy Volunteers / Human Immunodeficiency Virus (HIV) Infections1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV)2
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections2
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections1
1CompletedNot AvailableInfections, Human Immunodeficiency Virus and Hepatitis2
1CompletedNot AvailableInfections, Human Immunodeficiency Virus and Herpesviridae1
1CompletedBasic ScienceHuman Immunodeficiency Virus (HIV) Infections2
1CompletedOtherHIV-DDI1
1CompletedOtherHuman Immunodeficiency Virus (HIV) Infections1
1CompletedPreventionHealthy Adult Females1
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections4
1Not Yet RecruitingTreatmentHIV-1-infection / Tuberculosis1
1, 2RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2Active Not RecruitingTreatmentDolutegravir / Monotherapy / Primary HIV Infection / Treatment Efficacy1
2Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I1
2CompletedTreatmentDolutegravir / Human Immunodeficiency Virus (HIV) / Monotherapy / Treatment Efficacy1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentInfection, Human Immunodeficiency Virus I2
2RecruitingTreatmentHIV II Infection1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis1
2TerminatedTreatmentHIV-infection/Aids / Human Immunodeficiency Virus (HIV) Infections1
2TerminatedTreatmentInfection, Human Immunodeficiency Virus I1
2, 3RecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Pregnancy1
2, 3WithdrawnTreatmentHIV-infection/Aids1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections3
3Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I2
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
3CompletedTreatmentInfection, Human Immunodeficiency Virus I2
3No Longer AvailableNot AvailableHuman Immunodeficiency Virus (HIV)1
3Not Yet RecruitingTreatmentHIV Infection Primary1
3Not Yet RecruitingTreatmentHIV-1-infection / Pregnancy Related1
3Not Yet RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
3RecruitingTreatmentAcute HIV Infection1
3RecruitingTreatmentHIV-1-infection1
3RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
3RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections2
3RecruitingTreatmentInfection, Human Immunodeficiency Virus I3
3Unknown StatusTreatmentInfection, Human Immunodeficiency Virus I1
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV)4
4Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I1
4CompletedNot AvailableHuman Immunodeficiency Virus (HIV)1
4CompletedBasic ScienceHuman Immunodeficiency Virus (HIV)1
4CompletedPreventionHuman Immunodeficiency Virus (HIV)1
4CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
4Not Yet RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
4RecruitingOtherHIV-infection/Aids1
4RecruitingTreatmentAcquired Immune Deficiency Syndrome Virus1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections3
4RecruitingTreatmentInfection, Human Immunodeficiency Virus I1
4Unknown StatusTreatmentHuman Immunodeficiency Virus (HIV)1
Not AvailableActive Not RecruitingNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableActive Not RecruitingTreatmentChronic Infection / Human Immunodeficiency Virus (HIV)1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedOtherChronic Hepatitis C Infection / Human Immunodeficiency Virus (HIV)1
Not AvailableNot Yet RecruitingNot AvailableContraceptive Usage / Drug Interactions / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableRecruitingNot AvailableMinor Patient Treated by One or More Antiretroviral and for Which a Blood Test Has Been Performed1
Not AvailableRecruitingBasic ScienceHuman Immunodeficiency Virus (HIV)1
Not AvailableRecruitingTreatmentAcute HIV Infection / Human Immunodeficiency Virus (HIV)1
Not AvailableRecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral10 mg
TabletOral25 mg
TabletOral50 mg
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral50 mg
Tablet, film coatedOral50 mg/1
TabletOral
Tablet, film coatedOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9242986No2009-10-082029-10-08Us
US5905082Yes1996-11-182016-11-18Us
US6294540Yes1998-11-142018-11-14Us
US6417191Yes1996-09-282016-09-28Us
US8129385No2007-10-052027-10-05Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilitySlightly solubleFDA label
Predicted Properties
PropertyValueSource
Water Solubility0.0922 mg/mLALOGPS
logP0.98ALOGPS
logP1.1ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)8.7ChemAxon
pKa (Strongest Basic)0.28ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area99.18 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity102.77 m3·mol-1ChemAxon
Polarizability39.99 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as pyridinecarboxylic acids and derivatives. These are compounds containing a pyridine ring bearing a carboxylic acid group or a derivative thereof.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Pyridinecarboxylic acids and derivatives
Direct Parent
Pyridinecarboxylic acids and derivatives
Alternative Parents
2-heteroaryl carboxamides / Fluorobenzenes / Hydroxypyridines / 1,3-oxazinanes / Aryl fluorides / Vinylogous amides / Vinylogous acids / Tertiary carboxylic acid amides / Heteroaromatic compounds / Secondary carboxylic acid amides
show 9 more
Substituents
Pyridine carboxylic acid or derivatives / 2-heteroaryl carboxamide / Hydroxypyridine / Fluorobenzene / Halobenzene / 1,3-oxazinane / Aryl fluoride / Aryl halide / Monocyclic benzene moiety / Oxazinane
show 22 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
organofluorine compound, monocarboxylic acid amide, organic heterotricyclic compound (CHEBI:76010)

Targets

Kind
Protein
Organism
Human immunodeficiency virus 1
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Not Available
Gene Name
pol
Uniprot ID
Q7ZJM1
Uniprot Name
Integrase
Molecular Weight
32226.645 Da
References
  1. Hare S, Smith SJ, Metifiot M, Jaxa-Chamiec A, Pommier Y, Hughes SH, Cherepanov P: Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol. 2011 Oct;80(4):565-72. doi: 10.1124/mol.111.073189. Epub 2011 Jun 30. [PubMed:21719464]
  2. Waki K, Sugawara Y: Implications of integrase inhibitors for HIV-infected transplantation recipients: raltegravir and dolutegravir (S/GSK 1349572). Biosci Trends. 2011;5(5):189-91. [PubMed:22101373]
  3. Underwood MR, Johns BA, Sato A, Martin JN, Deeks SG, Fujiwara T: The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adults. J Acquir Immune Defic Syndr. 2012 Nov 1;61(3):297-301. doi: 10.1097/QAI.0b013e31826bfd02. [PubMed:22878423]
  4. Dooley KE, Sayre P, Borland J, Purdy E, Chen S, Song I, Peppercorn A, Everts S, Piscitelli S, Flexner C: Safety, tolerability, and pharmacokinetics of the HIV integrase inhibitor dolutegravir given twice daily with rifampin or once daily with rifabutin: results of a phase 1 study among healthy subjects. J Acquir Immune Defic Syndr. 2013 Jan 1;62(1):21-7. doi: 10.1097/QAI.0b013e318276cda9. [PubMed:23075918]
  5. Cottrell ML, Hadzic T, Kashuba AD: Clinical pharmacokinetic, pharmacodynamic and drug-interaction profile of the integrase inhibitor dolutegravir. Clin Pharmacokinet. 2013 Nov;52(11):981-94. doi: 10.1007/s40262-013-0093-2. [PubMed:23824675]
  6. Rathbun RC, Lockhart SM, Miller MM, Liedtke MD: Dolutegravir, a second-generation integrase inhibitor for the treatment of HIV-1 infection. Ann Pharmacother. 2014 Mar;48(3):395-403. doi: 10.1177/1060028013513558. Epub 2013 Nov 19. [PubMed:24259658]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function
Transcription factor that specifically binds to the octamer motif (5'-ATTTGCAT-3'). Regulates transcription in a number of tissues in addition to activating immunoglobulin gene expression. Modulate...
Gene Name
POU2F2
Uniprot ID
P09086
Uniprot Name
POU domain, class 2, transcription factor 2
Molecular Weight
51208.51 Da
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...

Components:

Drug created on November 11, 2013 14:17 / Updated on November 23, 2017 11:53