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Compound Detail

CHEMBL3

NICOTINE
💊 Approved Drug
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💊 Approved Drug
CN1CCC[C@H]1c1cccnc1

Basic Information

ChEMBL ID CHEMBL3
Name NICOTINE
Phase Approved
Structure Type MOL
InChI Key SNICXCGAKADSCV-JTQLQIEISA-N
Therapeutic ✓ Yes

Known Names

Habitrol Nicabate Nicoderm cq Nicopass Nicopatch Nicorette invisi Nicotine Nicotinell classic Nicotinell support Nicotinell tts 10 Nicotinell tts 20 Nicotinell tts 30 +14 more
56
Targets
560
Activities
4
Assay Types
21
PK Parameters
20
Publications
26
Known Names
20
Indications
1
Mechanisms

Molecular Properties

162.2
MW (Da)
1.85
ALogP
2
HBA
0
HBD
16.1
PSA (Ų)
0.63
QED
0
Ro5 Violations
1
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1984
Availability OTC
Chirality Single Enantiomer

Routes of Administration

Oral Topical

Flags

Natural Product
USAN Year 1985

Extended Properties

Molecular Formula C10H14N2
MW 162.24
Aromatic Rings 1
Heavy Atoms 12
NP-Likeness -0.41

Mechanism of Action

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

Indications

Tobacco Use Disorder Heart Failure Lung Neoplasms Marijuana Abuse Pulmonary Disease, Chronic Obstructive Severe Acute Respiratory Syndrome Severe Acute Respiratory Syndrome Smoking Smoking Cessation Uterine Cervical Neoplasms Alcohol Drinking Carcinoma Cognitive Dysfunction Depressive Disorder Parkinson Disease Postoperative Nausea and Vomiting Sarcoma Wounds and Injuries Aging Attention Deficit Disorder with Hyperactivity

ATC Classification

N07BA01
nicotine
Level 1: NERVOUS SYSTEM
Level 2: OTHER NERVOUS SYSTEM DRUGS

Activity Summary

Ki 363 meas. best 10.35
EC50 106 meas. best 9.0
IC50 71 meas. best 9.0
Kd 20 meas. best 11.0

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Neuronal acetylcholine receptor
CHEMBL2094110
Kd 11.0 7.66 0.0 7
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907589
Ki 10.35 8.6446 0.0 28
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907596
Ki 9.08 8.4425 0.8 81
Unchecked
CHEMBL612545
Ki 9.07 7.456 0.8 40
Unchecked
CHEMBL612545
Kd 9.05 6.3975 0.9 4
Acetylcholine receptor
CHEMBL2096975
IC50 9.0 8.7 1.0 2
Neuronal acetylcholine receptor; alpha3/beta2
CHEMBL1907587
Ki 9.0 7.5421 1.0 14
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907589
EC50 9.0 5.9132 1.0 25
Neuronal acetylcholine receptor
CHEMBL2094110
Ki 9.0 8.6264 1.0 11
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907589
IC50 8.92 6.7315 1.2 13
Neuronal nicotinic acetylcholine receptor
CHEMBL3350222
Ki 8.92 8.905 1.2 2
Mus musculus
CHEMBL375
Kd 8.85 8.85 1.4 1
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907596
IC50 8.78 8.6 1.6 2
Neuronal acetylcholine receptor subunit alpha-4
CHEMBL5569
Ki 8.72 8.72 1.9 1
Neuronal acetylcholine receptor subunit alpha-9
CHEMBL2585
IC50 8.62 8.62 2.4 1
Neuronal acetylcholine receptor
CHEMBL2094110
IC50 8.52 8.3125 3.0 4
Neuronal acetylcholine receptor subunit alpha-6/beta-3
CHEMBL3883329
Ki 8.48 8.48 3.3 1
Nicotinic acetylcholine receptor alpha-4/beta-2
CHEMBL3301382
Ki 8.46 8.46 3.5 1
Neuronal acetylcholine receptor; alpha3/beta2
CHEMBL2109234
IC50 8.42 8.42 3.8 1
Neuronal nicotinic acetylcholine receptor
CHEMBL3350222
IC50 8.4 8.4 4.0 1
Unchecked
CHEMBL612545
IC50 8.4 7.1867 4.0 12
Neuronal acetylcholine receptor; alpha3/beta4
CHEMBL1907594
Ki 8.3 6.5172 5.0 18
Neuronal acetylcholine receptor subunit alpha-9
CHEMBL2585
Kd 8.3 8.3 5.0 1
Neuronal acetylcholine receptor; alpha4/beta4
CHEMBL1907595
Ki 8.26 7.3787 5.5 23
Neuronal acetylcholine receptor; alpha2/beta2
CHEMBL1907592
Ki 8.26 8.0655 5.5 11
Neuronal acetylcholine receptor; alpha2/beta2
CHEMBL2109236
Ki 8.26 8.09 5.5 2
Neuronal acetylcholine receptor subunit alpha-4
CHEMBL4457
IC50 8.15 8.15 7.0 1
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907596
EC50 8.14 6.2585 7.3 13
Neuronal acetylcholine receptor subunit alpha-2
CHEMBL2584
Ki 7.92 7.92 12.0 1
Neuronal acetylcholine receptor subunit alpha-7
CHEMBL4980
IC50 7.8 7.8 16.0 1
Neuronal acetylcholine receptor; alpha4/beta4
CHEMBL1907591
Ki 7.64 7.346 23.0 5
Neuronal acetylcholine receptor; alpha3/beta2
CHEMBL2109234
Ki 7.54 7.435 29.0 4
Soluble acetylcholine receptor
CHEMBL1944497
Ki 7.52 6.4467 30.0 3
Rattus norvegicus
CHEMBL376
EC50 7.4 5.9 40.0 2
Neuronal acetylcholine receptor subunit alpha-3
CHEMBL3068
IC50 7.35 7.35 45.0 1
Acetylcholine-binding protein
CHEMBL6084
Ki 7.2 6.7675 63.1 8
Neuronal acetylcholine receptor; alpha2/beta4
CHEMBL2109230
Ki 7.16 7.0367 70.0 3
Neuronal acetylcholine receptor; alpha2/beta4
CHEMBL1907590
Ki 7.16 7.0583 70.0 12
Neuronal acetylcholine receptor subunit beta-4
CHEMBL2658
Ki 7.14 7.14 73.0 1
Neuronal acetylcholine receptor; alpha3/alpha6/beta2/beta3
CHEMBL2109233
IC50 7.07 7.07 84.8 1
Unchecked
CHEMBL612545
EC50 7.0 5.114 100.0 10
Neuronal acetylcholine receptor; alpha3/alpha6/beta2/beta3
CHEMBL2109233
EC50 6.9 6.9 127.0 1
Neuronal acetylcholine receptor subunit alpha-7
CHEMBL4980
Ki 6.89 6.1203 130.0 32
Neuronal acetylcholine receptor subunit alpha-3/beta-4
CHEMBL3885609
Ki 6.78 6.78 167.0 1
Striatum
CHEMBL613663
EC50 6.7 6.7 199.5 2
Neuronal acetylcholine receptor; alpha3/beta4
CHEMBL1907593
Ki 6.7 6.4696 199.5 24
Neuronal acetylcholine receptor subunit alpha-3
CHEMBL3068
Ki 6.66 6.66 220.0 1
Neuronal acetylcholine receptor subunit alpha-7
CHEMBL3365
Ki 6.61 6.465 244.0 2
Neuronal acetylcholine receptor; alpha3/beta4
CHEMBL1907594
EC50 6.54 5.07 290.0 11
Acetylcholine-binding protein
CHEMBL6084
Kd 6.5 6.44 316.2 3

Pharmacokinetic Data

Parameter Value Units Species
CL 18.0 mL.min-1.kg-1 Homo sapiens
CL 15.0 mL.min-1.kg-1 Homo sapiens
CL 18.0 mL.min-1.kg-1 Homo sapiens
CL 42.0 mL.min-1.kg-1 Canis lupus familiaris
CL 66.0 mL.min-1.kg-1 Rattus norvegicus
CL 14.0 mL.min-1.kg-1 Macaca
CL 18.0 mL.min-1.kg-1 Homo sapiens
CL 19.0 mL.min-1.kg-1 Homo sapiens
F 49.0 % Homo sapiens
Fu 0.95 - -
Fu 0.15 - -
Fu 0.95 - Homo sapiens
Fu 0.95 - Homo sapiens
Fu 0.95 - Homo sapiens
Ka 4700000.0 M-1 Rattus norvegicus
Ka 4400.0 M-1 Rattus norvegicus
MRT 2.4 hr Homo sapiens
T1/2 2.0 hr Homo sapiens
T1/2 2.0 hr Rattus norvegicus
T1/2 0.1 hr Mus musculus
T1/2 0.9 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Neuronal acetylcholine receptor Kd = 0.01 nM 11.0 Ability to enhance the binding of (+/-)-[3H]nicotine to the rat brain P2 fractio... 4032427
Neuronal acetylcholine receptor Kd = 0.022 nM 10.66 Compound was evaluated for ability to enhance the binding of (+/-)-[3H]nicotine ... 4032427
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.045 nM 10.35 Agonist activity at alpha4beta2 nAChR (unknown origin) 29751234
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.6 nM 9.22 Displacement of [3H]cytisine from human alpha4beta2 nAChR overexpressed in human... 23561269
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.84 nM 9.08 Binding affinity to Nicotinic acetylcholine receptor alpha4-beta2 using +/-[3H]e... 11855986
Unchecked Ki = 0.85 nM 9.07 Displacement of [3H]epibatidine from alpha4beta2* nAChR in Sprague-Dawley rat br... 22609074
Unchecked Kd = 0.89 nM 9.05 Binding affinity to Sprague-Dawley rat brain nAChR incubated for 90 min by scatc... 33120080
Unchecked Ki = 0.9 nM 9.05 Displacement of [3H]NMCI from nicotinic acetylcholine receptor 8496700
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.94 nM 9.03 Displacement of [3H]cytisine from Nicotinic acetylcholine receptor alpha4-beta2 ... 12190326
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.9333 nM 9.03 Displacement of [3H]cytisine from alpha-4-beta-2 in rat cerebral cortical membra... 17585748
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.94 nM 9.03 Displacement of [3H]cytisine from alpha-4-beta-2 in rat cerebral cortical membra... 17585748
Unchecked Ki = 0.9333 nM 9.03 Displacement of [3H]cytisine from neuronal nicotinic acetylcholine receptor in r... 17929796
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.94 nM 9.03 Displacement of [3H]cytisine from alpha4beta2 nAChR in rat brain membrane 19232492
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.94 nM 9.03 Displacement of [3H]cytisine from alpha4beta2 nicotinic acetylcholine receptor i... 19552432
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.95 nM 9.02 Inhibition of [3H]-nicotine binding to nicotinic acetylcholine receptor alpha4-b... 15908213
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 0.95 nM 9.02 Inhibition of [3H]nicotine binding to nicotinic acetylcholine receptor alpha4-be... 15887955
Acetylcholine receptor IC50 = 1.0 nM 9.0 Inhibition of [3H]MCC binding to torpedo electroplax membranes 3346870
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 1.0 nM 9.0 The compound was evaluated for percentage inhibition of binding of [3H]- nicotin... 9622546
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 1.0 nM 9.0 Inhibition of binding of [3H]nicotine to Nicotinic acetylcholine receptor alpha4... 9622546
Neuronal acetylcholine receptor; alpha4/beta2 Ki = 1.0 nM 9.0 Binding affinity towards alpha4-beta2 measured by using the inhibition of [3H]NI... 12467625

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885881 Rattus norvegicus 405
16472241 10.2174/1570163043334794 Hepatotoxicity 18
33120080 10.1016/j.bmc.2020.115820 Neuronal acetylcholine receptor; alpha4/beta2 17
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
4032427 10.1021/jm00147a021 Neuronal acetylcholine receptor 14
24581918 10.1016/j.bmcl.2014.02.008 NON-PROTEIN TARGET 12
16789751 10.1021/jm060230+ ADMET 10
23092294 10.1021/jm301177j Neuronal acetylcholine receptor; alpha4/beta2 10
- 10.6019/CHEMBL5303304 HEK-293T 9
20070106 10.1021/jm901371v Homo sapiens 8
- 10.1016/S0960-894X(01)80157-8 Rattus norvegicus 8
15920768 10.1002/jps.20373 ADMET 8
25408831 10.1021/ml500129k Neuronal acetylcholine receptor; alpha4/beta2 8
33120080 10.1016/j.bmc.2020.115820 Unchecked 7
- 10.6019/CHEMBL5303304 U2OS 7
20822184 10.1021/jm100765u Neuronal acetylcholine receptor; alpha4/beta2 6
23116890 10.1016/j.bmcl.2012.10.012 Neuronal acetylcholine receptor; alpha4/beta2 6
22171543 10.1021/jm201157c Neuronal acetylcholine receptor; alpha4/beta2 6
23734673 10.1021/jm400510u Neuronal acetylcholine receptor; alpha4/beta2 6
18710918 10.1128/aac.00523-08 NON-PROTEIN TARGET 6

Data from ChEMBL 36 via Core Engine