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Compound Detail

CHEMBL1076903

VARENICLINE
💊 Approved Drug
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💊 Approved Drug
c1cnc2cc3c(cc2n1)[C@@H]1CNC[C@H]3C1

Basic Information

ChEMBL ID CHEMBL1076903
Name VARENICLINE
Phase Approved
Structure Type MOL
InChI Key JQSHBVHOMNKWFT-DTORHVGOSA-N
Therapeutic ✓ Yes

Known Names

CP-526,555 CP-526555 Vareniclina Varenicline
18
Targets
91
Activities
3
Assay Types
4
PK Parameters
20
Publications
4
Known Names
20
Indications
1
Mechanisms

Molecular Properties

211.3
MW (Da)
1.80
ALogP
3
HBA
1
HBD
37.8
PSA (Ų)
0.72
QED
0
Ro5 Violations
0
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2006
Availability Prescription
Chirality Achiral

Routes of Administration

Oral Topical

Flags

Natural Product
USAN Stem -nicline
USAN Year 2003

Extended Properties

Molecular Formula C13H13N3
MW 211.27
Aromatic Rings 2
Heavy Atoms 16
NP-Likeness 0.25

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Neuronal acetylcholine receptor; alpha4/beta2 partial agonist PARTIAL AGONIST Neuronal acetylcholine receptor; alpha4/beta2

Indications

Eye Diseases Tobacco Use Disorder Acute Coronary Syndrome Alcoholism Dry Eye Syndromes Lung Neoplasms Lung Neoplasms Neoplasms Smoking Cessation Alcohol Drinking Alzheimer Disease Amphetamine-Related Disorders Cocaine-Related Disorders Friedreich Ataxia Machado-Joseph Disease Marijuana Abuse Parkinson Disease Psychotic Disorders Schizophrenia Substance-Related Disorders

ATC Classification

N07BA03
varenicline
Level 1: NERVOUS SYSTEM
Level 2: OTHER NERVOUS SYSTEM DRUGS
S01XA28
varenicline
Level 1: SENSORY ORGANS
Level 2: OPHTHALMOLOGICALS

Activity Summary

Ki 60 meas. best 10.4
EC50 20 meas. best 10.22
IC50 11 meas. best 7.41

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907589
Ki 10.4 8.76 0.0 10
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907596
Ki 10.3 9.9467 0.1 6
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907589
EC50 10.22 6.8363 0.1 8
Unchecked
CHEMBL612545
Ki 9.92 8.732 0.1 10
Neuronal acetylcholine receptor; alpha2/beta2
CHEMBL1907592
Ki 9.66 9.49 0.2 2
Neuronal acetylcholine receptor; alpha2/beta2
CHEMBL2109236
Ki 9.32 9.32 0.5 2
Neuronal acetylcholine receptor; alpha3/beta2
CHEMBL1907587
Ki 8.72 8.66 1.9 2
Neuronal acetylcholine receptor; alpha3/beta2
CHEMBL2109234
Ki 8.6 8.6 2.5 1
Neuronal acetylcholine receptor; alpha4/beta4
CHEMBL1907595
Ki 7.82 7.3225 15.0 4
Neuronal acetylcholine receptor; alpha4/beta4
CHEMBL1907591
Ki 7.55 7.255 28.0 2
Neuronal acetylcholine receptor subunit alpha-7
CHEMBL4980
Ki 7.49 7.245 32.5 8
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907589
IC50 7.41 6.7671 38.9 7
Neuronal acetylcholine receptor; alpha3/beta4
CHEMBL1907594
Ki 7.4 7.0025 39.6 4
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907596
EC50 7.34 7.34 46.0 1
Neuronal acetylcholine receptor subunit alpha-6/beta-3
CHEMBL3883329
EC50 7.34 7.34 46.0 1
Neuronal acetylcholine receptor; alpha2/beta4
CHEMBL1907590
Ki 7.15 7.09 71.0 2
Neuronal acetylcholine receptor; alpha3/beta4
CHEMBL1907593
Ki 7.07 6.7225 86.0 4
Neuronal acetylcholine receptor; alpha2/beta4
CHEMBL2109230
Ki 7.03 7.03 94.0 1
Unchecked
CHEMBL612545
IC50 7.03 7.03 94.0 1
Neuronal acetylcholine receptor; alpha3/beta4
CHEMBL1907594
IC50 6.96 6.96 110.0 1
Neuronal acetylcholine receptor subunit alpha-7
CHEMBL2492
Ki 6.9 6.9 125.0 1
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907596
IC50 6.7 6.7 200.0 2
Unchecked
CHEMBL612545
EC50 6.02 5.34 950.0 2
Neuronal acetylcholine receptor; alpha3/beta4
CHEMBL1907594
EC50 5.85 5.255 1400.0 2
Neuronal acetylcholine receptors; alpha-3/beta-4, alpha-5, beta-2
CHEMBL2221346
EC50 5.66 5.66 2200.0 1
Acetylcholine receptor; alpha1/beta1/delta/gamma
CHEMBL1907588
Ki 5.09 5.09 8200.0 1
Neuronal acetylcholine receptor subunit alpha-7
CHEMBL4980
EC50 4.75 4.75 18000.0 2
Neuronal acetylcholine receptor; alpha3/beta4
CHEMBL1907593
EC50 4.68 4.54 21000.0 3

Pharmacokinetic Data

Parameter Value Units Species
Fu 0.897 - Rattus norvegicus
Fu 0.709 - Rattus norvegicus
T1/2 5.4 hr Mus musculus
T1/2 1.4 hr Mus musculus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.04 nM 10.4 Displacement of [3H]cytisine from human alpha4beta2 nAChR expressed in CHOK1 cel... 32026697
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.05 nM 10.3 Displacement of [3H]epibatidine from rat alpha4beta2 nACHR 22148173
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.06 nM 10.22 Binding affinity to rat cortex Nicotinic acetylcholine receptor alpha4-beta2 usi... 16171993
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.06 nM 10.22 Binding affinity to alpha4beta2 nAChR in rat cortex 23121096
Neuronal acetylcholine receptor; alpha4/beta2 EC50 = 0.06 nM 10.22 Partial agonist activity at alpha4beta 2 nAChR 22591063
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.11 nM 9.96 Binding affinity for human Nicotinic acetylcholine receptor alpha4-beta2 express... 16171993
Unchecked Ki = 0.12 nM 9.92 Displacement of [3H]-epibatidine from alpha4beta2* nAChR in Sprague-Dawley rat c... 24428686
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.12 nM 9.92 [3H]-Epibatidine Radioligand Binding Assay: Briefly, cultured cells at >80% conf... -
Unchecked Ki = 0.12 nM 9.92 [3H]Epibatidine Binding Assay: Adult male rat cerebral cortices (Pelfreeze Biolo... -
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.12 nM 9.92 Displacement of [3H]-epibatidine from alpha4beta2 nAChR in rat cerebral cortex h... 26233800
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.12 nM 9.92 Displacement of [3H]-Epibatidine from rat alpha4beta2 nACHR expressed in HEK293 ... 23540678
Unchecked Ki = 0.12 nM 9.92 Displacement of [3H]epibatidine from rat cerebral cortex alpha4beta2* nAChR incu... 22742586
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.12 nM 9.92 Displacement of [3H]epibatidine from alpha-4-beta-2 nAChR in rat cerebral cortex 17964169
Unchecked Ki = 0.12 nM 9.92 [3H]-Epibatidine Radioligand Binding Assay: Briefly, cultured cells at >80% conf... -
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.13 nM 9.89 Displacement of [3H]epibatidine from human alpha4beta2 nAChR after 4 hrs by cell... 24047231
Neuronal acetylcholine receptor; alpha2/beta2 Ki = 0.22 nM 9.66 Displacement of [3H]epibatidine from rat alpha2beta2 nAChR expressed in HEK293 c... 24047231
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.295 nM 9.53 Displacement of [3H]epibatidine from alpha4beta2 nicotinic receptor expressed in... 20663668
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.4 nM 9.4 Binding affinity to alpha4beta2 nAChR 23092294
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.4 nM 9.4 Displacement of [3H]epibatidine from rat forebrain alpha4beta2 nAChR by competit... 25408831
Unchecked Ki = 0.4 nM 9.4 Agonist activity at alpha4beta2* nAChR (unknown origin) 24901260

Literature References

PubMed DOI Target Context # Activities
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
- 10.6019/CHEMBL5303304 U2OS 8
23092294 10.1021/jm301177j Neuronal acetylcholine receptor; alpha4/beta2 8
17964169 10.1016/j.bmc.2007.10.027 Mus musculus 7
23540678 10.1021/jm4000374 Mustela putorius furo 7
16171993 10.1016/j.bmcl.2005.08.035 Neuronal acetylcholine receptor; alpha4/beta2 7
22742586 10.1021/jm300575y Mus musculus 6
- 10.6019/CHEMBL5303304 HEK-293T 6
24428686 10.1021/jm401602p Mus musculus 6
26233800 10.1016/j.bmc.2015.07.021 Mus musculus 6
24901260 10.1021/jm401937a Neuronal acetylcholine receptor; alpha4/beta2 6
22148173 10.1021/jm201301h Neuronal acetylcholine receptor; alpha3/beta4 5
23540678 10.1021/jm4000374 Neuronal acetylcholine receptor; alpha3/beta4 4
22148173 10.1021/jm201301h Neuronal acetylcholine receptors; alpha-3/beta-4, alpha-5, beta-2 4
24047231 10.1021/jm4008455 Neuronal acetylcholine receptor; alpha4/beta2 4
26233800 10.1016/j.bmc.2015.07.021 Neuronal acetylcholine receptor; alpha4/beta2 4
23540678 10.1021/jm4000374 Neuronal acetylcholine receptor; alpha4/beta2 4
24047231 10.1021/jm4008455 Neuronal acetylcholine receptor; alpha3/beta4 4
24428686 10.1021/jm401602p Neuronal acetylcholine receptor; alpha4/beta2 3
23540678 10.1021/jm4000374 Unchecked 3

Data from ChEMBL 36 via Core Engine