Skip to main content
Free research Free research Free compound review with research home and workspace preview
Quick search ChEMBL 36
Compound Detail

CHEMBL462605

PITOLISANT
💊 Approved Drug
Enter ChEMBL ID:
Free Research Context This compound will appear in recent viewed items on the research home for this browser.
Research home View demo workspace
💊 Approved Drug
Clc1ccc(CCCOCCCN2CCCCC2)cc1
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL462605
Name PITOLISANT
Phase Approved
Structure Type MOL
InChI Key NNACHAUCXXVJSP-UHFFFAOYSA-N
Therapeutic ✓ Yes

Known Names

BF-2.649 BF-2649 Bf2.649 HBS-101 Pitolisant Tiprolisant Wakix Wakix, europe
10
Targets
55
Activities
4
Assay Types
1
PK Parameters
20
Publications
8
Known Names
10
Indications
1
Mechanisms

Molecular Properties

295.9
MW (Da)
4.17
ALogP
2
HBA
0
HBD
12.5
PSA (Ų)
0.67
QED
0
Ro5 Violations
8
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2016
Availability Prescription
Chirality Achiral

Routes of Administration

Oral

Flags

Natural Product First in Class
USAN Stem -isant
USAN Year 2018

Extended Properties

Molecular Formula C17H26ClNO
MW 295.85
Aromatic Rings 1
Heavy Atoms 20
NP-Likeness -1.15

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Histamine H3 receptor inverse agonist INVERSE AGONIST Histamine H3 receptor ✓ ✓

Indications

Idiopathic Hypersomnia Narcolepsy Narcolepsy Parkinson Disease Alcoholism Child Development Disorders, Pervasive Prader-Willi Syndrome Schizophrenia Kidney Diseases Substance-Related Disorders

ATC Classification

N07XX11
pitolisant
Level 1: NERVOUS SYSTEM
Level 2: OTHER NERVOUS SYSTEM DRUGS

Activity Summary

Ki 45 meas. best 9.8
IC50 6 meas. best 7.92
EC50 3 meas. best 8.82
Kd 1 meas. best 8.25

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Histamine H3 receptor
CHEMBL264
 Ki 9.8 8.4347 0.2 34
Histamine H3 receptor
CHEMBL5076
 Ki 9.8 9.8 0.2 2
Sigma non-opioid intracellular receptor 1
CHEMBL4153
 Ki 9.3 9.3 0.5 1
Histamine H3 receptor
CHEMBL264
 EC50 8.82 8.46 1.5 2
Histamine H3 receptor
CHEMBL5076
 EC50 8.82 8.82 1.5 1
Histamine H3 receptor
CHEMBL5076
 Kd 8.25 8.25 5.6 1
Sigma intracellular receptor 2
CHEMBL4105864
 Ki 8.19 8.19 6.5 1
Histamine H3 receptor
CHEMBL264
 IC50 7.92 7.3567 12.0 3
Histamine H3 receptor
CHEMBL3263
 Ki 7.85 7.85 14.0 1
Histamine H3 receptor
CHEMBL4124
 Ki 7.77 7.77 17.0 4
Unchecked
CHEMBL612545
 Ki 7.72 7.72 19.0 1
Histamine H1 receptor
CHEMBL231
 Ki 5.94 5.94 1148.2 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
 IC50 5.77 5.77 1700.0 1
Cholinesterase
CHEMBL5763
 IC50 5.08 5.08 8400.0 2

Pharmacokinetic Data

Parameter Value Units Species
T1/2 10.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Histamine H3 receptor Ki = 0.16 nM 9.8 Antagonist activity at human histamine H3 receptor expressed in HEK293 cells by ... 19329325
Histamine H3 receptor Ki = 0.16 nM 9.8 Binding affinity to human H3R assessed as inhibition constant 36155354
Histamine H3 receptor Ki = 0.16 nM 9.8 Antagonist activity at recombinant human H3 receptor expressed in CHO-K1 cell me... 32911308
Histamine H3 receptor Ki = 0.16 nM 9.8 Inhibition of Guinea Pig Ileum H3R 31404862
Histamine H3 receptor Ki = 0.16 nM 9.8 Antagonist activity at human histamine H3 receptor expressed in HEK293 cells by ... 19456097
Histamine H3 receptor Ki = 0.3 nM 9.52 Binding affinity to human H3R 33261900
Histamine H3 receptor Ki = 0.3 nM 9.52 Binding affinity to human histamine H3 receptor 28372935
Histamine H3 receptor Ki = 0.3 nM 9.52 Inhibition of human H3 receptor 29723785
Sigma non-opioid intracellular receptor 1 Ki = 0.5 nM 9.3 Displacement of [3H](+)-pentazocine from sigma 1 receptor in guinea pig brain me... 37418295
Histamine H3 receptor Ki = 0.912 nM 9.04 Binding affinity in Nluc-hH3R assessed in HEK293 cells by NanoBRET binding assay 34309390
Histamine H3 receptor EC50 = 1.5 nM 8.82 Inverse agonist activity at human H3R 36155354
Histamine H3 receptor EC50 = 1.5 nM 8.82 Antagonist activity at human histamine H3 receptor expressed in CHO-K1 cells by ... 19329325
Histamine H3 receptor Ki = 1.549 nM 8.81 Displacement of [3H]UR-MN259 from SP-FLAG tagged human histamine H3 receptor exp... 37974943
Histamine H3 receptor Ki = 2.4 nM 8.62 Displacement of [125I]Iodoproxyfran from human histamine H3 receptor expressed i... 19329325
Histamine H3 receptor Ki = 2.512 nM 8.6 Binding affinity to histamine H3 receptor (unknown origin) 37974943
Histamine H3 receptor Ki = 2.512 nM 8.6 Antagonist activity at histamine H3 receptor (unknown origin) 34695709
Histamine H3 receptor Ki = 2.512 nM 8.6 Binding affinity in Nluc-hH3R assessed in HEK293T cells by NanoBRET binding assa... 34309390
Histamine H3 receptor Ki = 2.512 nM 8.6 Displacement of [125I]iodoproxyfan from human recombinant histamine H3 receptor ... 18774720
Histamine H3 receptor Ki = 2.512 nM 8.6 Displacement of Clobenpropit-BODIPY-630/650 from Nluc-tagged human histamine H3 ... 37974943
Histamine H3 receptor Ki = 2.7 nM 8.57 Displacement of [125I]iodoproxyfan human histamine H3 receptor 20728354

Literature References

PubMed DOI Target Context # Activities
19329325 10.1016/j.bmc.2009.03.014 Histamine H3 receptor 8
28888822 10.1016/j.bmcl.2017.08.060 Histamine H3 receptor 5
32105981 10.1016/j.ejmech.2020.112150 Histamine H3 receptor 5
37974943 10.1021/acsmedchemlett.3c00413 Histamine H3 receptor 4
29681486 10.1016/j.bmc.2018.04.023 Histamine H3 receptor 3
37468498 10.1038/s41467-023-40064-9 Nuclear receptor subfamily 1 group I member 2 3
37468498 10.1038/s41467-023-40064-9 Muscarinic acetylcholine receptor M2 2
28372935 10.1016/j.bmc.2017.03.031 Histamine H3 receptor 2
31669851 10.1016/j.ejmech.2019.111785 Cholinesterase 2
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
36542960 10.1016/j.bmc.2022.117132 Histamine H3 receptor 2
37468498 10.1038/s41467-023-40064-9 Alpha-1A adrenergic receptor 2
33261900 10.1016/j.ejmech.2020.113041 Histamine H3 receptor 2
19577344 10.1016/j.ejmech.2009.06.007 Histamine H3 receptor 2
34695709 10.1016/j.bmc.2021.116462 Histamine H3 receptor 2
32882609 10.1016/j.ejmech.2020.112743 Histamine H3 receptor 2
37468498 10.1038/s41467-023-40064-9 5-hydroxytryptamine receptor 1A 2
37468498 10.1038/s41467-023-40064-9 Progesterone receptor 2
34309390 10.1021/acs.jmedchem.1c01089 Histamine H3 receptor 2
37468498 10.1038/s41467-023-40064-9 Gamma-aminobutyric acid receptor subunit alpha-1 2

Data from ChEMBL 36 via Core Engine