VARENICLINE

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Trade Names
Synonyms
Status
Molecule Category Free-form
ATC N07BA03
UNII W6HS99O8ZO

Structure

InChI Key JQSHBVHOMNKWFT-UHFFFAOYSA-N
Smiles c1cnc2cc3c(cc2n1)C1CNCC3C1
InChI
InChI=1S/C13H13N3/c1-2-16-13-5-11-9-3-8(6-14-7-9)10(11)4-12(13)15-1/h1-2,4-5,8-9,14H,3,6-7H2

Physicochemical Descriptors

Property Name Value
Molecular Formula C13H13N3
Molecular Weight 211.27
AlogP 1.8
Hydrogen Bond Acceptor 3.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 0.0
Polar Surface Area 37.81
Molecular species BASE
Aromatic Rings 2.0
Heavy Atoms 16.0

Bioactivity

Mechanism of Action Action Reference
Neuronal acetylcholine receptor; alpha4/beta2 partial agonist PARTIAL AGONIST FDA
Protein: Neuronal acetylcholine receptor; alpha4/beta2
Description: Neuronal acetylcholine receptor subunit beta-2
Organism : Homo sapiens
P17787 ENSG00000160716
Protein: Neuronal acetylcholine receptor; alpha4/beta2
Description: Neuronal acetylcholine receptor subunit alpha-4
Organism : Homo sapiens
P43681 ENSG00000101204
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Ion channel Ligand-gated ion channel Nicotinic acetylcholine receptor Nicotinic acetylcholine receptor alpha subunit
0-1400 39-50000 - 0-3540 38-38
Ion channel Ligand-gated ion channel Nicotinic acetylcholine receptor Nicotinic acetylcholine receptor beta subunit
0-1400 39-50000 - 0-3540 38-38
Ion channel Ligand-gated ion channel Nicotinic acetylcholine receptor Nicotinic acetylcholine receptor delta subunit
- - - 8200 -
Ion channel Ligand-gated ion channel Nicotinic acetylcholine receptor Nicotinic acetylcholine receptor gamma subunit
- - - 8200 -
Transporter Electrochemical transporter SLC superfamily of solute carriers SLC21/SLCO family of organic anion transporting polypeptides
- - - - 1
Assay Description Organism Bioactivity Reference
Binding affinity to rat cortex Nicotinic acetylcholine receptor alpha4-beta2 using [3H]nicotine Rattus norvegicus 0.06 nM
Binding affinity for human Nicotinic acetylcholine receptor alpha4-beta2 expressed in HEK 293 cells using [3H]nicotine Homo sapiens 0.11 nM
Binding affinity to human Nicotinic acetylcholine receptor alpha4-beta2 expressed in IMR32 cells using [3H]epibatidine Homo sapiens 240.0 nM
Binding affinity to human Nicotinic acetylcholine receptor alpha4-beta2 expressed in IMR32 cells using [3H]alpha-bungarotoxin Homo sapiens 617.0 nM
Percent inhibition against 10 uM nicotine binding to human Nicotinic acetylcholine receptor alpha4-beta2 expressed in Xenopus oocytes at 10 uM Homo sapiens 32.0 %
Displacement of [3H]epibatidine from alpha-4-beta-2 nAChR in rat cerebral cortex Rattus norvegicus 0.12 nM
Displacement of [125I]iodoMLA from alpha-7 nAChR in rat cerebral cortex Rattus norvegicus 32.5 nM
Displacement of [3H]epibatidine from alpha4beta2 nicotinic receptor expressed in human HEK293 cells None 0.295 nM
Displacement of [3H]epibatidine from alpha3beta4 nicotinic receptor expressed in human HEK293 cells None 74.7 nM
Displacement of [3H]epibatidine from alpha6/4beta4 nicotinic receptor expressed in human HEK293 cells None 89.0 nM
Displacement of [3H]epibatidine from alpha7 nicotinic receptor expressed in human HEK293 cells None 125.0 nM
Agonist activity at rat alpha6beta2 nAChR assessed as [3H]dopamine release by beta counting Rattus norvegicus 46.0 nM
Agonist activity at rat alpha4beta2 nAChR assessed as [3H]dopamine release by beta counting Rattus norvegicus 46.0 nM
Partial agonist activity at alpha4beta 2 nAChR Homo sapiens 0.06 nM
Binding affinity to rat alpha7 nACHR at 10 uM Rattus norvegicus 125.0 nM
Antagonist activity at rat alpha4beta2 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced response at 100 uM after 2 to 6 days by two electrode voltage clamp assay Rattus norvegicus 38.0 %
Displacement of [125I]iodoMLA from rat cerebral cortex alpha7 nAChR at 50 nM incubated for 2 hrs by microplate scintillation assay Rattus norvegicus 32.5 nM
Displacement of [3H]epibatidine from rat cerebral cortex alpha4beta2* nAChR incubated for 4 hrs by liquid scintillation assay Rattus norvegicus 0.12 nM
Inhibition of human liver OATP1B1 expressed in HEK293 Flp-In cells assessed as reduction in E17-betaG uptake at 20 uM by scintillation counting Homo sapiens 24.7 %
Inhibition of human liver OATP1B3 expressed in HEK293 Flp-In cells assessed as reduction in [3H]E17-betaG uptake at 20 uM incubated for 5 mins by scintillation counting Homo sapiens 0.8 %
Inhibition of human liver OATP2B1 expressed in HEK293 Flp-In cells assessed as reduction in [3H]E3S uptake at 20 uM incubated for 5 mins by scintillation counting Homo sapiens 27.3 %
Displacement of [3H]epibatidine from rat alpha3beta4 nACHR Rattus norvegicus 86.0 nM
Displacement of [3H]epibatidine from rat alpha4beta2 nACHR Rattus norvegicus 0.05 nM
Displacement of [3H]epibatidine from rat alpha4beta4 nACHR Rattus norvegicus 110.0 nM
Inhibition of human alpha4beta2 nACHR expressed in SH-EP1 cells by 86Rb+ efflux assay Homo sapiens 110.0 nM
Binding affinity to rat alpha7 nAChR expressed in Xenopus laevis oocytes Rattus norvegicus 300.0 nM
Antagonist activity at human alpha4beta2 nAChR expressed in human SH-EP1 cells assessed as inhibition of 86Rb+ efflux preincubated for 10 mins by liquid scintillation counting Homo sapiens 38.9 nM Antagonist activity at human alpha4beta2 nAChR expressed in human SH-EP1 cells assessed as inhibition of 86Rb+ efflux preincubated for 10 mins by liquid scintillation counting Homo sapiens 39.0 nM
Binding affinity to alpha4beta4 nAChR None 110.0 nM
Binding affinity to alpha4beta2 nAChR None 0.4 nM
Binding affinity to alpha3beta4 nAChR None 86.0 nM
Binding affinity to alpha4beta2 nAChR in rat cortex Rattus norvegicus 0.06 nM
Desensitization of human alpha4beta2 nACHR expressed in HEK293 cells assessed as inhibition of 86Rb+ efflux preincubated for 10 mins measured after 2 hrs by liquid scintillation counting analysis Homo sapiens 94.0 nM
Agonist activity at human alpha4beta2 nACHR expressed in HEK293 cells assessed as stimulation of 86Rb+ efflux after 2 hrs by liquid scintillation counting analysis Homo sapiens 950.0 nM
Displacement of [3H]-Epibatidine from rat alpha7 nACHR expressed in HEK293 cell membranes by liquid scintillation counting analysis Rattus norvegicus 37.0 nM
Displacement of [3H]-Epibatidine from rat alpha4beta4 nACHR expressed in HEK293 cell membranes by liquid scintillation counting analysis Rattus norvegicus 28.0 nM
Displacement of [3H]-Epibatidine from rat alpha4beta2 nACHR expressed in HEK293 cell membranes by liquid scintillation counting analysis Rattus norvegicus 0.12 nM
Displacement of [3H]-Epibatidine from rat alpha3beta4 nACHR expressed in HEK293 cell membranes by liquid scintillation counting analysis Rattus norvegicus 390.0 nM
Displacement of [3H]-Epibatidine from rat alpha3beta2 nACHR expressed in HEK293 cell membranes by liquid scintillation counting analysis Rattus norvegicus 2.5 nM
Displacement of [3H]-Epibatidine from rat alpha2beta4 nACHR expressed in HEK293 cell membranes by liquid scintillation counting analysis Rattus norvegicus 94.0 nM
Displacement of [3H]-Epibatidine from rat alpha2beta2 nACHR expressed in HEK293 cell membranes by liquid scintillation counting analysis Rattus norvegicus 0.48 nM
Antagonist activity at human alpha4beta2 nAChR assessed as inhibition of nicotine-induced [86Rb+] efflux preincubated for 10 mins before nicotine exposure by cell-based liquid scintillation counting Homo sapiens 94.0 nM
Agonist activity at human alpha4beta2 nAChR assessed as stimulation of [86Rb+] efflux after 2 mins by cell-based liquid scintillation counting Homo sapiens 950.0 nM
Displacement of [3H]epibatidine from nAChR in rat forebrain Rattus norvegicus 0.71 nM
Displacement of [3H]epibatidine from rat alpha7 nAChR expressed in HEK293 cells after 4 hrs Rattus norvegicus 62.0 nM
Displacement of [3H]epibatidine from rat alpha4beta4 nAChR expressed in HEK293 cells after 4 hrs Rattus norvegicus 15.0 nM
Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell-based assay Homo sapiens 0.13 nM
Displacement of [3H]epibatidine from rat alpha3beta4 nAChR expressed in HEK293 cells after 4 hrs Rattus norvegicus 460.0 nM
Displacement of [3H]epibatidine from rat alpha3beta2 nAChR expressed in HEK293 cells after 4 hrs Rattus norvegicus 1.9 nM
Displacement of [3H]epibatidine from rat alpha2beta4 nAChR expressed in HEK293 cells after 4 hrs Rattus norvegicus 71.0 nM
Displacement of [3H]epibatidine from rat alpha2beta2 nAChR expressed in HEK293 cells after 4 hrs Rattus norvegicus 0.22 nM
Antagonist activity at rat alpha4beta2 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced current by two-electrode voltage clamp electrophysiological analysis Rattus norvegicus 200.0 nM
Displacement of [3H]-epibatidine from alpha4beta2* nAChR in Sprague-Dawley rat cerebral cortex after 4 hrs by liquid scintillation counting analysis Rattus norvegicus 0.12 nM
Displacement of [3H]epibatidine from rat forebrain alpha3beta4 nAChR by competition binding assay Rattus norvegicus 86.0 nM
Displacement of [3H]epibatidine from rat forebrain alpha4beta2 nAChR by competition binding assay Rattus norvegicus 0.4 nM
Displacement of [3H]epibatidine from rat forebrain alpha4beta4 nAChR by competition binding assay Rattus norvegicus 110.0 nM
Inactivation of alpha4beta2* nAChR high affinity site (unknown origin) expressed in xenopus oocytes by electrophysiology method Homo sapiens 70.0 nM
Agonist activity at alpha4beta2* nAChR (unknown origin) Homo sapiens 0.4 nM
Agonist activity at human alpha4beta2 nAChR expressed in xenopus oocytes by electrophysiology method Homo sapiens 2.3 nM
Displacement of [3H]-epibatidine from alpha4beta2 nAChR in rat cerebral cortex homogenates after 4 hrs by liquid scintillation counting Rattus norvegicus 0.12 nM
Antagonist activity at rat alpha4beta2 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced mean current response by measuring remaining current at 100 uM by two-electrode voltage clamp electrophysiology assay relative to control Rattus norvegicus 38.0 %
Antagonist activity at rat alpha4beta2 nAChR expressed in Xenopus laevis oocytes assessed as inhibition of acetylcholine-induced mean current response by two-electrode voltage clamp electrophysiology assay Rattus norvegicus 200.0 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 22.78 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.17 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus -0.17 %

Cross References

Resources Reference
ChEMBL CHEMBL1396
DrugBank DB01273
FDA SRS W6HS99O8ZO
Guide to Pharmacology 5459
PubChem 5310966
SureChEMBL SCHEMBL225687
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