Identification

Name
Dolutegravir
Accession Number
DB08930
Type
Small Molecule
Groups
Approved
Description

Dolutegravir is a HIV-1 intergrase inhibitor that blocks the strand transfer step of the integration of the viral genome into the host cell (INSTI).[1] The effect of this drug has no homology in human host cells which gives it an excellent tolerability and minimal toxicity.[11] Dolutegravir was developed by ViiV Healthcare and FDA approved on August 12, 2013.[15] On November 21, 2017, dolutegravir, in combination with rilpivirine, was approved as part of the first complete treatment regimen with only two drugs for the treatment of adults with HIV-1 named Juluca.[16]

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
TivicayTablet10 mgOralViiV Healthcare ULC2017-06-20Not applicableCanada
TivicayTablet50 mgOralViiV Healthcare ULC2013-11-08Not applicableCanada
TivicayTablet, film coated25 mg/1OralViiV Healthcare Company2016-06-09Not applicableUs
TivicayTablet, film coated50 mg/1OralA-S Medication Solutions2013-08-13Not applicableUs50090 135520180913 8702 njvfz6
TivicayTablet, film coated50 mgOralViiV Healthcare ULC2014-01-16Not applicableEu
TivicayTablet, film coated50 mg/1OralREMEDYREPACK INC.2018-10-06Not applicableUs
TivicayTablet, film coated10 mg/1OralViiV Healthcare Company2016-06-09Not applicableUs
TivicayTablet25 mgOralViiV Healthcare ULC2017-06-20Not applicableCanada
TivicayTablet, film coated50 mgOralViiV Healthcare ULC2014-01-16Not applicableEu
TivicayTablet, film coated50 mg/1OralViiV Healthcare Company2013-08-13Not applicableUs49702 0228 13 nlmimage10 d23d694b
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
JulucaDolutegravir Sodium (50 mg/1) + Rilpivirine Hydrochloride (25 mg/1)Tablet, film coatedOralViiV Healthcare Company2017-11-21Not applicableUs
TriumeqDolutegravir Sodium (50 mg/1) + Abacavir Sulfate (600 mg/1) + Lamivudine (300 mg/1)Tablet, film coatedOralGlaxo Operations UK Ltd2014-08-222017-12-21Us
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 Company2014-08-22Not applicableUs
TriumeqDolutegravir Sodium (50 mg/1) + Abacavir Sulfate (600 mg/1) + Lamivudine (300 mg/1)Tablet, film coatedOralA-S Medication Solutions2014-08-22Not applicableUs
TriumeqDolutegravir Sodium (50 mg/1) + Abacavir Sulfate (600 mg/1) + Lamivudine (300 mg/1)Tablet, film coatedOralA-S Medication Solutions2014-08-22Not applicableUs
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[8.4.0.0^{3,8}]tetradeca-10,13-diene-13-carboxamide
SMILES
[H][C@]12CN3C=C(C(=O)NCC4=CC=C(F)C=C4F)C(=O)C(O)=C3C(=O)N1[C@H](C)CCO2

Pharmacology

Indication

Dolutegravir is indicated in combination with other antiretroviral agents for the treatment of patients with HIV-1 infection that comply with the characteristics of being adults or children aged 12 years and older and present at least a weight of 40 kg.[7] The FDA combination therapy approval of dolutegravir and rilpivirine is indicated for adults with HIV-1 infections whose virus is currently suppressed (< 50 copies/ml) on a stable regimen for at least six months, without history of treatment failure and no known substitutions associated to resistance to any of the two components of the therapy.[16]

Associated Conditions
Pharmacodynamics

HIV-1 infected subjects on dolutegravir monotherapy demonstrated rapid and dose-dependent reduction of antiviral activity with declines of HIV-1 RNA copies per ml. The antiviral response was maintained for 3 to 4 days after the last dose.[3] The sustained response obtained in clinical trials indicates that dolutegravir has a tight binding and longer dissociative half-life providing it a high barrier to resistance.[A31343] The combination therapy (ripivirine and dolutegravir) presented the same viral suppression found in previous three-drug therapies without integrase strand transfer inhibitor mutations or rilpivirine resistance.[L1033]

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 of retroviral DNA integration in the host cell. The strand transfer step is essential in the HIV replication cycle and results in the 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.[4]

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, 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, and C24 is 3.49 mcg/mL, 46 mcg.h/mL, and 0.90 mcg/mL respectively.[1]

Volume of distribution

The administration of a dose of 50 mg of dolutegravir presents an apparent volume of distribution of 17.4 L. The median dolutegravir concentration in CSF was 18 ng/mL after 2 weeks of treatment.[1]

Protein binding

Dolutegravir is highly protein bound to human plasma proteins reaching a percentage 98.9% of the administered dose.[1]

Metabolism

Dolutegravir is highly metabolized through three main pathways and it forms no long-lived metabolites. The first pathway is defined by the glucuronidation by UGT1A1, the second pathway by carbon oxidation by CYP3A4 and the third pathway is what appears to be a sequential oxidative defluorination and glutathione conjugation. The main metabolite found in blood plasma is the ether glucuronide form (M2) and its chemical properties disrupt its ability to bind metal ions, therefore, it is inactive.[12]

Route of elimination

When a single oral dose of dolutegravir is given, nearly all complete dose is recovered in a proportion of 53% excreted unchanged in the feces and 31% excreted in urine. The renal eliminated recovered dose consists of ether glucuronide of dolutegravir (18.9%), a metabolite formed by oxidation at the benzylic carbon (3.0%), a hydrolytic N-dealkylation product (3.6%) and unchanged drug (< 1%).[12]

Half life

The half-life of dolutegravir is 14 hours.[1]

Clearance

The apparent clearance rate of dultegravir is 1.0 L/h.[Label]

Toxicity

There was no significant increases in drug-related neoplasms or in genotoxic effects or in mating or fertility effects.[13]

Affected organisms
  • Humans and other mammals
  • 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
DrugInteraction
AbemaciclibThe serum concentration of Dolutegravir can be increased when it is combined with Abemaciclib.
AcetaminophenThe serum concentration of Dolutegravir can be increased when it is combined with Acetaminophen.
Acetylcysteine zincAcetylcysteine zinc can cause a decrease in the absorption of Dolutegravir resulting in a reduced serum concentration and potentially a decrease in efficacy.
AcyclovirThe excretion of Acyclovir can be decreased when combined with Dolutegravir.
Adefovir DipivoxilThe excretion of Adefovir Dipivoxil can be decreased when combined with Dolutegravir.
AdenineThe metabolism of Dolutegravir can be decreased when combined with Adenine.
AfatinibThe serum concentration of Dolutegravir can be increased when it is combined with Afatinib.
AgmatineThe serum concentration of Agmatine can be increased when it is combined with Dolutegravir.
AlbendazoleThe serum concentration of Dolutegravir can be increased when it is combined with Albendazole.
AldosteroneThe serum concentration of Dolutegravir can be decreased when it is combined with Aldosterone.
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]
  11. Dow DE, Bartlett JA: Dolutegravir, the Second-Generation of Integrase Strand Transfer Inhibitors (INSTIs) for the Treatment of HIV. Infect Dis Ther. 2014 Dec;3(2):83-102. doi: 10.1007/s40121-014-0029-7. Epub 2014 Jun 24. [PubMed:25134686]
  12. Castellino S, Moss L, Wagner D, Borland J, Song I, Chen S, Lou Y, Min SS, Goljer I, Culp A, Piscitelli SC, Savina PM: Metabolism, excretion, and mass balance of the HIV-1 integrase inhibitor dolutegravir in humans. Antimicrob Agents Chemother. 2013 Aug;57(8):3536-46. doi: 10.1128/AAC.00292-13. Epub 2013 May 13. [PubMed:23669385]
  13. Elzi L, Erb S, Furrer H, Cavassini M, Calmy A, Vernazza P, Gunthard H, Bernasconi E, Battegay M: Adverse events of raltegravir and dolutegravir. AIDS. 2017 Aug 24;31(13):1853-1858. doi: 10.1097/QAD.0000000000001590. [PubMed:28692533]
  14. Adams JL, Greener BN, Kashuba AD: Pharmacology of HIV integrase inhibitors. Curr Opin HIV AIDS. 2012 Sep;7(5):390-400. doi: 10.1097/COH.0b013e328356e91c. [PubMed:22789987]
  15. ViiV Healthcare News [Link]
  16. FDA News and Events [Link]
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
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 AvailableHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
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)1
1CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections4
1Not Yet RecruitingTreatmentHIV-1-infection / Tuberculosis Infection1
1RecruitingTreatmentHepatic Impairment / HIV-1-infection1
1, 2RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2Active Not RecruitingTreatmentDolutegravir / Monotherapy / Primary HIV Infection / Treatment Efficacy1
2Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections / Tuberculosis Infection1
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
2RecruitingTreatmentHIV-1-infection1
2RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
2TerminatedTreatmentInfection, Human Immunodeficiency Virus I1
2, 3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) / Pregnancy1
2, 3WithdrawnTreatmentHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
3Active Not RecruitingTreatmentHIV-1-infection1
3Active Not RecruitingTreatmentHIV-1-infection / Pregnancy Related1
3Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections4
3Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I5
3CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
3CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections3
3CompletedTreatmentInfection, Human Immunodeficiency Virus I3
3No Longer AvailableNot AvailableHuman Immunodeficiency Virus (HIV)1
3Not Yet RecruitingTreatmentPrimary HIV Infection1
3RecruitingTreatmentAcute HIV Infection / Chronic Infection With HIV1
3RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections2
3RecruitingTreatmentInfection, Human Immunodeficiency Virus I1
4Active Not RecruitingOtherHuman Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
4Active Not RecruitingTreatmentAcquired Immune Deficiency Syndrome Virus1
4Active Not RecruitingTreatmentHuman Immunodeficiency Virus (HIV)1
4Active Not RecruitingTreatmentInfection, Human Immunodeficiency Virus I1
4CompletedBasic ScienceHuman Immunodeficiency Virus (HIV)1
4CompletedPreventionHuman Immunodeficiency Virus (HIV)1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV)3
4CompletedTreatmentHuman Immunodeficiency Virus Type 1 (HIV-1)1
4Not Yet RecruitingTreatmentHuman Immunodeficiency Virus (HIV) Infections1
4RecruitingTreatmentHIV-1-infection / Solid Organ Transplant1
4RecruitingTreatmentHuman Immunodeficiency Virus (HIV)2
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)1
Not AvailableCompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableCompletedOtherHepatitis C Viral Infection / Human Immunodeficiency Virus (HIV)1
Not AvailableRecruitingNot AvailableContraceptive Usage / Drug Drug Interaction (DDI) / Human Immunodeficiency Virus (HIV) Infections1
Not AvailableRecruitingNot AvailableHuman 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
US7125879No2002-08-092022-08-09Us
US6838464No2001-02-262021-02-26Us
US8080551No2003-04-112023-04-11Us
US8101629No2002-08-092022-08-09Us
US7067522No1999-12-202019-12-20Us
US8129385No2007-10-052027-10-05Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)190-193ºCMSDS
water solubilitySlightly solubleFDA label
logP2.2 MSDS
pKa8.2MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0922 mg/mLALOGPS
logP0.98ALOGPS
logP1.1ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)10.1ChemAxon
pKa (Strongest Basic)-0.51ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area99.18 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity102.77 m3·mol-1ChemAxon
Polarizability40 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 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:
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Adams JL, Greener BN, Kashuba AD: Pharmacology of HIV integrase inhibitors. Curr Opin HIV AIDS. 2012 Sep;7(5):390-400. doi: 10.1097/COH.0b013e328356e91c. [PubMed:22789987]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Quaternary ammonium group transmembrane transporter activity
Specific Function
Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
Gene Name
SLC22A2
Uniprot ID
O15244
Uniprot Name
Solute carrier family 22 member 2
Molecular Weight
62579.99 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da

Drug created on November 11, 2013 14:17 / Updated on November 13, 2018 08:04