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Compound Detail

CHEMBL289469

GRANISETRON
💊 Approved Drug
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💊 Approved Drug
CN1C2CCCC1CC(NC(=O)c1nn(C)c3ccccc13)C2

Basic Information

ChEMBL ID CHEMBL289469
Name GRANISETRON
Phase Approved
Structure Type MOL
InChI Key MFWNKCLOYSRHCJ-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

APF-530 APF530 BRL 43694 BRL-43694 Granisetron LY-278584 Sancuso Sustol
14
Targets
80
Activities
4
Assay Types
11
PK Parameters
20
Publications
8
Known Names
16
Indications
1
Mechanisms

Molecular Properties

312.4
MW (Da)
2.32
ALogP
4
HBA
1
HBD
50.2
PSA (Ų)
0.93
QED
0
Ro5 Violations
2
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 1993
Availability Prescription
Chirality Achiral

Routes of Administration

Oral Parenteral Topical

Flags

Natural Product
USAN Stem -setron
USAN Year 1991

Extended Properties

Molecular Formula C18H24N4O
MW 312.42
Aromatic Rings 2
Heavy Atoms 23
NP-Likeness -1.06

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Serotonin 3a (5-HT3a) receptor antagonist ANTAGONIST 5-hydroxytryptamine receptor 3A

Indications

Nausea Nausea Neoplasms Neoplasms Postoperative Nausea and Vomiting Postoperative Nausea and Vomiting Postoperative Nausea and Vomiting Vomiting Carcinoma, Hepatocellular Pain Uterine Cervical Neoplasms Gastroparesis Glioma Leukemia, Mast-Cell Lymphoma Pruritus

ATC Classification

A04AA02
granisetron
Level 1: ALIMENTARY TRACT AND METABOLISM
Level 2: ANTIEMETICS AND ANTINAUSEANTS

Activity Summary

Ki 28 meas. best 9.6
Kd 25 meas. best 10.7
EC50 16 meas. best 7.13
IC50 11 meas. best 8.55

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Serotonin 3 (5-HT3) receptor
CHEMBL2094132
Kd 10.7 9.4167 0.0 6
Serotonin 3 (5-HT3) receptor
CHEMBL2094116
Kd 10.6 10.6 0.0 1
Unchecked
CHEMBL612545
Kd 9.96 9.96 0.1 1
5-hydroxytryptamine receptor 3B
CHEMBL3895
Kd 9.8 9.574 0.2 5
5-hydroxytryptamine receptor 3A
CHEMBL1899
Kd 9.72 9.331 0.2 10
Serotonin 3 (5-HT3) receptor
CHEMBL2111332
Kd 9.7 9.7 0.2 1
Serotonin 3 (5-HT3) receptor
CHEMBL2094116
Ki 9.6 9.0253 0.3 19
Cavia porcellus
CHEMBL369
Kd 9.2 9.2 0.6 1
Unchecked
CHEMBL612545
Ki 9.12 9.12 0.8 1
5-hydroxytryptamine receptor 3A
CHEMBL1899
Ki 8.84 8.6933 1.4 3
Serotonin 3 (5-HT3) receptor
CHEMBL2094132
Ki 8.68 8.15 2.1 2
NG108-15
CHEMBL613828
IC50 8.55 8.55 2.8 1
Unchecked
CHEMBL612545
IC50 8.47 8.47 3.4 1
5-hydroxytryptamine receptor 3A
CHEMBL3666
Ki 8.4 8.4 4.0 1
5-hydroxytryptamine receptor 3A
CHEMBL1899
EC50 7.13 6.8 74.0 9
Unchecked
CHEMBL612545
EC50 6.89 5.9033 130.0 6
Serotonin 3 (5-HT3) receptor
CHEMBL2111332
EC50 6.3 6.3 500.0 1
Serotonin 3 (5-HT3) receptor
CHEMBL2094116
IC50 5.75 5.75 1760.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 5.43 5.424 3715.3 5
Solute carrier family 22 member 2
CHEMBL1743122
IC50 5.37 5.37 4300.0 1
Multidrug and toxin extrusion protein 1
CHEMBL1743126
IC50 5.3 5.3 5000.0 1
Neuronal acetylcholine receptor; alpha4/beta2
CHEMBL1907589
Ki 4.42 4.42 38000.0 1
Neuronal acetylcholine receptor subunit alpha-3
CHEMBL3068
Ki 4.17 4.17 67000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 11.0 mL.min-1.kg-1 Homo sapiens
CL 9.1 mL.min-1.kg-1 Homo sapiens
CL 8.1 mL.min-1.kg-1 Homo sapiens
CL 9.1 mL.min-1.kg-1 Homo sapiens
CL 9.1 mL.min-1.kg-1 Homo sapiens
F 60.0 % Homo sapiens
Fu 0.35 - Homo sapiens
Fu 0.35 - Homo sapiens
MRT 6.7 hr Homo sapiens
T1/2 5.0 hr -
T1/2 5.2 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Serotonin 3 (5-HT3) receptor Kd = 0.01995 nM 10.7 Potency at neuronal 5-hydroxytryptamine 3 receptor in the rabbit heart 2342053
Serotonin 3 (5-HT3) receptor Kd = 0.02512 nM 10.6 5-hydroxytryptamine 3 receptor antagonist activity was confirmed by its ability ... 2362270
Serotonin 3 (5-HT3) receptor Kd = 0.07943 nM 10.1 Evaluated for the antagonistic activity against 5-hydroxytryptamine 3 receptor i... -
Unchecked Kd = 0.11 nM 9.96 Binding affinity to human 5-HT3B receptor E170A mutant after 24 hrs by liquid sc... 24128813
Serotonin 3 (5-HT3) receptor Kd = 0.1259 nM 9.9 Evaluated for the antagonistic activity against 5-hydroxytryptamine 3 receptor i... -
Serotonin 3 (5-HT3) receptor Kd = 0.1259 nM 9.9 Binding affinity to 5-hydroxytryptamine 3 receptor of neuronal in the afferent r... 2342053
5-hydroxytryptamine receptor 3B Kd = 0.16 nM 9.8 Binding affinity to human 5-HT3B receptor I183A mutant after 24 hrs by liquid sc... 24128813
5-hydroxytryptamine receptor 3A Kd = 0.19 nM 9.72 Binding affinity to human 5-HT3A receptor S163T mutant after 24 hrs by liquid sc... 24128813
Serotonin 3 (5-HT3) receptor Kd = 0.2 nM 9.7 Binding affinity to human wild type 5-HT3A/5-HT3B receptor expressed in HEK293 c... 24128813
5-hydroxytryptamine receptor 3B Kd = 0.2 nM 9.7 Binding affinity to human 5-HT3B receptor Y143A mutant after 24 hrs by liquid sc... 24128813
5-hydroxytryptamine receptor 3B Kd = 0.22 nM 9.66 Binding affinity to human 5-HT3B receptor H73A mutant after 24 hrs by liquid sci... 24128813
Serotonin 3 (5-HT3) receptor Ki = 0.2512 nM 9.6 Displacement of [3H]granisetron from 5-hydroxytryptamine 3 receptor of rat corte... -
5-hydroxytryptamine receptor 3B Kd = 0.25 nM 9.6 Binding affinity to human 5-HT3B receptor W90C mutant after 24 hrs by liquid sci... 24128813
Serotonin 3 (5-HT3) receptor Ki = 0.35 nM 9.46 Inhibition of [3H]granisetron binding to 5-hydroxytryptamine 3 receptor of rat c... 10229626
Serotonin 3 (5-HT3) receptor Ki = 0.35 nM 9.46 Displacement of [3H]granisetron from 5-hydroxytryptamine 3 receptor of rat corti... 15887964
Serotonin 3 (5-HT3) receptor Ki = 0.35 nM 9.46 Ability to displace [3H]granisetron specifically bound to 5-hydroxytryptamine 3 ... 9513601
Serotonin 3 (5-HT3) receptor Ki = 0.35 nM 9.46 In vitro affinity for 5-hydroxytryptamine 3 (5-HT3) receptor by displacement of ... 9341912
5-hydroxytryptamine receptor 3A Kd = 0.36 nM 9.44 Binding affinity to human 5-HT3A receptor S163A mutant after 24 hrs by liquid sc... 24128813
5-hydroxytryptamine receptor 3A Kd = 0.37 nM 9.43 Binding affinity to human 5-HT3A receptor D165A mutant after 24 hrs by liquid sc... 24128813
5-hydroxytryptamine receptor 3A Kd = 0.41 nM 9.39 Binding affinity to human 5-HT3A receptor Y73S mutant after 24 hrs by liquid sci... 24128813

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885881 Rattus norvegicus 461
24128813 10.1016/j.bmc.2013.09.028 5-hydroxytryptamine receptor 3A 24
16472241 10.2174/1570163043334794 Hepatotoxicity 18
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
24128813 10.1016/j.bmc.2013.09.028 Unchecked 8
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
20070106 10.1021/jm901371v Homo sapiens 8
2362270 10.1021/jm00169a016 Serotonin 3 (5-HT3) receptor 6
8230119 10.1021/jm00074a009 Rattus norvegicus 6
9685241 10.1021/jm9801004 Mus musculus 5
2342053 10.1021/jm00168a011 Serotonin 3 (5-HT3) receptor 5
24128813 10.1016/j.bmc.2013.09.028 5-hydroxytryptamine receptor 3B 5
9341912 10.1021/jm970060o Serotonin 3 (5-HT3) receptor 4
18426954 10.1124/dmd.108.020479 ADMET 4
37468498 10.1038/s41467-023-40064-9 Alpha-1A adrenergic receptor 4
1312602 10.1021/jm00083a014 Mustela putorius furo 4
37468498 10.1038/s41467-023-40064-9 Cannabinoid receptor 1 4
17391967 10.1016/j.bmc.2007.02.054 5-hydroxytryptamine receptor 3A 3
2258903 10.1021/jm00174a013 Rattus norvegicus 3

Data from ChEMBL 36 via Core Engine