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Varenicline

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Also known as CP-526,555CP-526555Vareniclina(+/-)-vareniclineSID174007164

Summary

Varenicline (CHEMBL1076903) is an approved small-molecule nicotinic acetylcholine receptor agonist (ATC N07BA03) targeting CHRNA3 and CHRNA4; indicated across 21 conditions including nicotine dependence and eye disorder.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: N07BA03 (+1 more)
  • Targets: 2 (CHRNA3, CHRNA4)
  • Indications: 21 conditions
  • Clinical trials: 256
  • Chemistry: 211.26 Da · C13H13N3

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL1076903
NameVarenicline
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID5310966
ChEBICHEBI:84500
ATCN07BA03, S01XA28
Molecular formulaC13H13N3
Molecular weight211.26
InChIKeyJQSHBVHOMNKWFT-DTORHVGOSA-N

SMILES: C1[C@@H]2CNC[C@H]1C3=CC4=NC=CN=C4C=C23

IUPAC name: (1S,12R)-5,8,14-triazatetracyclo[10.3.1.02,11.04,9]hexadeca-2,4,6,8,10-pentaene

ChEBI definition: An organic heterotetracyclic compound that acts as a partial agonist for nicotinic cholinergic receptors and is used (in the form of its tartate salt) as an aid to giving up smoking.

Pharmacological roles (ChEBI): nicotinic acetylcholine receptor agonist, serotonergic agonist.

Also known as: CP-526,555, CP-526555, Vareniclina, Varenicline, varenicline, (+/-)-varenicline, SID174007164, VARENICLINE

Parent form; salt/anhydrous children: CHEMBL5303393, CHEMBL5316216, CHEMBL6067972

Patent coverage: 1,591 distinct patent families (5,807 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 5,805 (100%) 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

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
CHRNA3nicotinic acetylcholine receptor α3 subunitAgonist7.40%P32297
CHRNA4nicotinic acetylcholine receptor α4 subunitAgonist10.40.2%P43681

Broader ChEMBL bioactivity targets: 20 (assay-derived). Sample: Neuronal acetylcholine receptor subunit alpha-4, 5-hydroxytryptamine receptor 3A, Neuronal acetylcholine receptor; alpha3/beta2, Acetylcholine receptor; alpha1/beta1/delta/gamma, Neuronal acetylcholine receptor; alpha4/beta2, Neuronal acetylcholine receptor; alpha2/beta4, Neuronal acetylcholine receptor; alpha4/beta4, Neuronal acetylcholine receptor; alpha2/beta2, Neuronal acetylcholine receptor; alpha3/beta4, Neuronal acetylcholine receptor; alpha3/beta4.

Bioactivity

ChEMBL activities: 73 potent at pChembl ≥ 5 of 81 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
CHRNB210.4Ki0.04nMCHEMBL_ACT_20604952
P0948310.3Ki0.05nMCHEMBL_ACT_12081013
CHRNB210.22EC500.06nMCHEMBL_ACT_10965843
CHRNB210.22Ki0.06nMCHEMBL_ACT_12662624
P0948310.22Ki0.06nMCHEMBL_ACT_1615574
CHRNB29.96Ki0.11nMCHEMBL_ACT_1615570
P094839.92Ki0.12nMCHEMBL_ACT_12654968
P094839.92Ki0.12nMCHEMBL_ACT_15689680
CHRNB29.92Ki0.12nMCHEMBL_ACT_17760731
P094839.92Ki0.12nMCHEMBL_ACT_2130920
CHRNB29.89Ki0.13nMCHEMBL_ACT_13830885
P123899.66Ki0.22nMCHEMBL_ACT_13830961
CHRNB29.53Ki0.29nMCHEMBL_ACT_3376099
CHRNB29.4Ki0.4nMCHEMBL_ACT_12162740
P094839.4Ki0.4nMCHEMBL_ACT_15093333
P123899.32Ki0.48nMCHEMBL_ACT_12654965
CHRNB29.32Ki0.48nMCHEMBL_ACT_17760686
CHRNB29.32Ki0.48nMCHEMBL_ACT_27654233
P047578.72Ki1.9nMCHEMBL_ACT_13830923
CHRNB28.64EC502.3nMCHEMBL_ACT_15023483
P047578.6Ki2.5nMCHEMBL_ACT_12654962
CHRNB28.6Ki2.5nMCHEMBL_ACT_17760708
P094837.82Ki15nMCHEMBL_ACT_13830866
P094837.55Ki28nMCHEMBL_ACT_12654938
CHRNB47.55Ki28nMCHEMBL_ACT_17760743
Q059417.49Ki32.5nMCHEMBL_ACT_12092077
Q059417.49Ki32.5nMCHEMBL_ACT_17760216
Q059417.49Ki32.5nMCHEMBL_ACT_2130924
Q059417.43Ki37nMCHEMBL_ACT_12654935
Q059417.43Ki37nMCHEMBL_ACT_17760754

Target pathways

Aggregated over 2 target gene(s): CHRNA3, CHRNA4.

Top Reactome pathways

9 total, by targets touching each:

PathwayTargetsGenes
Neurotransmitter receptors and postsynaptic signal transmission2CHRNA3, CHRNA4
Transmission across Chemical Synapses2CHRNA3, CHRNA4
Neuronal System2CHRNA3, CHRNA4
Acetylcholine binding and downstream events2CHRNA3, CHRNA4
Presynaptic nicotinic acetylcholine receptors2CHRNA3, CHRNA4
Postsynaptic nicotinic acetylcholine receptors2CHRNA3, CHRNA4
Highly sodium permeable postsynaptic acetylcholine nicotinic receptors2CHRNA3, CHRNA4
Highly calcium permeable postsynaptic nicotinic acetylcholine receptors2CHRNA3, CHRNA4
Highly calcium permeable nicotinic acetylcholine receptors2CHRNA3, CHRNA4

Dominant GO biological processes

GO termTargets
monoatomic ion transport2
signal transduction2
synaptic transmission, cholinergic2
neuromuscular synaptic transmission2
monoatomic ion transmembrane transport2
response to nicotine2
behavioral response to nicotine2
regulation of membrane potential2
membrane depolarization2
excitatory postsynaptic potential2
acetylcholine receptor signaling pathway2
presynaptic modulation of chemical synaptic transmission2
regulation of smooth muscle contraction1
nervous system development1
locomotory behavior1

Indications & clinical

Indications

21 indications (2 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).

IndicationTrial phaseMONDOEFO
nicotine dependence4MONDO:0008575EFO:0003768
eye disorder4MONDO:0005328EFO:0003966
lung carcinoma3MONDO:0005138EFO:0001071
acute coronary syndrome3MONDO:0005542EFO:0005672
lung neoplasm3MONDO:0021117MONDO:0008903
dry eye syndrome3MONDO:0006733EFO:1000906
alcohol abuse3MONDO:0002046MONDO:0007079
neoplasm3MONDO:0005070MONDO:0004992
cocaine dependence2MONDO:0005186EFO:0002610
drug dependence2MONDO:0005303EFO:0003890
methamphetamine dependence2MONDO:0005419EFO:0004701
schizoaffective disorder2MONDO:0005487EFO:0005411
Machado-Joseph disease2MONDO:0007182Orphanet:98757
cannabis dependence2MONDO:0005689EFO:0007191
substance-related disorder2MONDO:0002494MONDO:0002491
Alzheimer disease2MONDO:0004975MONDO:0004975
Parkinson disease2MONDO:0005180MONDO:0005180
Friedreich ataxia2MONDO:0100339MONDO:0100339

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

Clinical trials

Total trials: 256.

Phase distribution

PhaseTrials
PHASE473
PHASE252
Not specified52
PHASE337
PHASE2/PHASE315
PHASE114
EARLY_PHASE17
PHASE1/PHASE26

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02162849PHASE4ACTIVE_NOT_RECRUITINGReward Sensitivity and Pharmacotherapy for Smoking Cessation
NCT03495024PHASE4RECRUITINGSmoking Cessation With Varenicline in Schizophrenia: Antipsychotic-Induced Neurological Symptoms as Correlates
NCT04604509PHASE4RECRUITINGNicotine Replacement Therapy, Counseling, Varenicline, and Bupropion for Smoking Cessation, the PISCES I Trial
NCT05694637PHASE4ENROLLING_BY_INVITATIONBotswana Smoking and Abstinence Reinforcement Trial
NCT06474299PHASE4RECRUITINGThe Avenues Study: Dual Use Cessation
NCT06688539PHASE4RECRUITINGE-cigarette Cessation in Adults Who Co-use Cannabis
NCT06832085PHASE4RECRUITINGCombination Nicotine Replacement Therapy, Cytisine, or Varenicline for Smoking Cessation
NCT06966362PHASE4NOT_YET_RECRUITINGVarenicline for Smoking Reduction in Veterans Not Ready To Quit
NCT07145866PHASE4NOT_YET_RECRUITINGVarenicline and Accelerated Transcranial Magnetic Stimulation (TMS) for Quitting Nicotine Use (Pilot Study)
NCT07606625PHASE4RECRUITINGOcular Surface Health and Tear Film Stability With a Nasal Spray Dry Eye Treatment
NCT00492349PHASE4COMPLETEDVarenicline Adjunctive Treatment in Schizophrenia
NCT00548470PHASE4COMPLETEDVarenicline Effects In Schizophrenic Smokers
NCT00621777PHASE4COMPLETEDA Study of Varenicline for Prevention of Relapse to Smoking in Patients With Schizophrenia or Bipolar Disorder
NCT00691483PHASE4COMPLETEDRandomized Study Comparing the Efficacy and Safety of Varenicline Tartrate to Placebo in Smoking Cessation When Subjects Are Allowed to Set Their Own Quit Date
NCT00702793PHASE4WITHDRAWNSafety and Tolerability of Varenicline in Schizophrenia (SATOVA)
NCT00727103PHASE4COMPLETEDVarenicline Treatment in Alcohol and Nicotine Dependent Patients With Schizophrenia
NCT00749944PHASE4COMPLETEDAssessing Neuropsychiatric Symptoms Including Depression, Anxiety, Irritability, and Suicidal Thoughts or Behavior in Subjects Quitting Smoking on Varenicline Tartrate or Placebo
NCT00781755PHASE4WITHDRAWNTreating Schizophrenic Smokers: Effects on Craving, Cues and Withdrawal
NCT00802919PHASE4COMPLETEDVarenicline for Cognitive Deficits and Cigarette Smoking in Schizophrenia - Efficacy and Predictors
NCT00828113PHASE4COMPLETEDLong-term Varenicline Treatment for Smoking Cessation
NCT00879177PHASE4COMPLETEDSmoking Study With Behavioral Therapy for Hypertensive Patients
NCT00889720PHASE4COMPLETEDA Pilot Study Of Smoking Cessation Treatment Including Varenicline In Patients Scheduled For Planned Surgery
NCT00907218PHASE4TERMINATEDChantix in Adult Smokers With Attention Deficit Hyperactivity Disorder (ADHD)
NCT00937508PHASE4UNKNOWNSmoking Cessation Program in the Preadmission Clinic
NCT00944554PHASE4COMPLETEDRelapse Prevention With Varenicline
NCT00948155PHASE4COMPLETEDMeasuring Smoking Behaviors While Using Varenicline
NCT00948649PHASE4COMPLETEDEffects of Chantix on Relapse Prevention for Smoking Cessation
NCT00959972PHASE4COMPLETEDVarenicline Versus Transdermal Nicotine Patch for Smoking Cessation in Patients With Coronary Heart Disease
NCT01010204PHASE4COMPLETEDVarenicline Treatment for Smoking Cessation in Patients With Bipolar Disorder
NCT01023659PHASE4COMPLETEDDistribution of Bupropion and Varenicline to Increase Smoking Cessation Attempts
NCT01027754PHASE4COMPLETEDSmoking Cessation Treatment for Methadone Maintenance Patients
NCT01078298PHASE4COMPLETEDSafety And Efficacy Of 12 Weeks Of Varenicline For Smoking Cessation In Smokers With Depression
NCT01228175PHASE4COMPLETEDEffectiveness of Varenicline: Testing Individual Differences
NCT01244061PHASE4COMPLETEDA Multi-National Study To Assess How Effective And Safe The Smoking Cessation Medicine Varenicline Is In Smokers Who Have Already Tried Varenicline In The Past As A Prescription Medicine From Their Usual Healthcare Provider
NCT01286584PHASE4COMPLETEDVarenicline in Drug Treatment
NCT01330043PHASE4COMPLETEDExtended Treatment for Smoking Cessation
NCT01474265PHASE4COMPLETEDSympathovagal Balance in Smoking Cessation
NCT01538394PHASE4COMPLETEDClinical Trial to Evaluate the Efficacy of Smoking Cessation
NCT01553084PHASE4COMPLETEDA Comparative Effectiveness & Long Term Health Study in Wisconsin Smokers
NCT01639560PHASE4COMPLETEDVarenicline for Light Smokers

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 6 clinical and 36 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

132 molecules share ≥1 primary target. Top 60 by shared-target count:

MoleculeSourceStatusShared targets
ACETYLCHOLINEChEMBL + PubChemPhase 4 (approved)CHRNA3, CHRNA4
BUPROPIONChEMBLPhase 4 (approved)CHRNA3, CHRNA4
GRANISETRONChEMBLPhase 4 (approved)CHRNA3, CHRNA4
MECAMYLAMINEChEMBLPhase 4 (approved)CHRNA3, CHRNA4
NICOTINEChEMBLPhase 4 (approved)CHRNA3, CHRNA4
ONDANSETRONChEMBLPhase 4 (approved)CHRNA3, CHRNA4
TROPISETRONChEMBLPhase 4 (approved)CHRNA3, CHRNA4
CYTISINICLINEChEMBL + PubChemPhase 3 (approved)CHRNA3, CHRNA4
DEXMECAMYLAMINEChEMBLPhase 3CHRNA3, CHRNA4
ALTINICLINEChEMBLPhase 2CHRNA3, CHRNA4
AZD1446ChEMBLPhase 2CHRNA3, CHRNA4
GTS-21ChEMBLPhase 2CHRNA3, CHRNA4
RADAFAXINEChEMBLPhase 2CHRNA3, CHRNA4
RIVANICLINEChEMBLPhase 2CHRNA3, CHRNA4
SOFINICLINEChEMBLPhase 2CHRNA3, CHRNA4
STILONIUM IODIDEChEMBLPhase 2CHRNA3, CHRNA4
TEBANICLINEChEMBLPhase 2CHRNA3, CHRNA4
CRIZOTINIBChEMBL + PubChemPhase 4 (approved)CHRNA4
RIFAMPINChEMBL + PubChemPhase 4 (approved)CHRNA4
ANISOTROPINEChEMBLPhase 4 (approved)CHRNA4
ATRACURIUMChEMBLPhase 4 (approved)CHRNA4
AZELASTINEChEMBLPhase 4 (approved)CHRNA4
CARBAMOYLCHOLINEChEMBLPhase 4 (approved)CHRNA4
CHLOROPROCAINEChEMBLPhase 4 (approved)CHRNA4
CHLORPHENTERMINEChEMBLPhase 4 (approved)CHRNA4
DAUNORUBICINChEMBLPhase 4 (approved)CHRNA4
DIPHEMANILChEMBLPhase 4 (approved)CHRNA4
EPALRESTATChEMBLPhase 4 (approved)CHRNA4
FENTANYLChEMBLPhase 4 (approved)CHRNA4
ILOPERIDONEChEMBLPhase 4 (approved)CHRNA4
MEDAZEPAMChEMBLPhase 4 (approved)CHRNA4
MOXISYLYTEChEMBLPhase 4 (approved)CHRNA4
NIMESULIDEChEMBLPhase 4 (approved)CHRNA4
NITAZOXANIDEChEMBLPhase 4 (approved)CHRNA4
OXYPERTINEChEMBLPhase 4 (approved)CHRNA4
PALBOCICLIBChEMBLPhase 4 (approved)CHRNA4
PALONOSETRONChEMBLPhase 4 (approved)CHRNA4
PONATINIBChEMBLPhase 4 (approved)CHRNA4
PYRVINIUMChEMBLPhase 4 (approved)CHRNA4
RIFAXIMINChEMBLPhase 4 (approved)CHRNA4
SERTINDOLEChEMBLPhase 4 (approved)CHRNA4
SUNITINIBChEMBLPhase 4 (approved)CHRNA4
THIORIDAZINEChEMBLPhase 4 (approved)CHRNA4
VANDETANIBChEMBLPhase 4 (approved)CHRNA4
ZIMELDINEChEMBLPhase 4 (approved)CHRNA4
CINITAPRIDEChEMBLPhase 3CHRNA4
DIACEREINChEMBLPhase 3CHRNA4
PYRONARIDINEChEMBLPhase 3CHRNA4
RADOTINIBChEMBLPhase 3CHRNA4
TRIMEBUTINEChEMBLPhase 3CHRNA4
18-METHOXYCORONARIDINEChEMBLPhase 2CHRNA3
ALCURONIUMChEMBLPhase 2CHRNA4
ANABASEINEChEMBLPhase 2CHRNA3
AZD0328ChEMBLPhase 2CHRNA4
BRADANICLINEChEMBLPhase 2CHRNA4
CLEBOPRIDEChEMBLPhase 2CHRNA4
ISPRONICLINEChEMBLPhase 2CHRNA4
LOBELINEChEMBLPhase 2CHRNA4
MEQUITAZINEChEMBLPhase 2CHRNA4
NEMONAPRIDEChEMBLPhase 2CHRNA4

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot