Pitolisant

Summary

Pitolisant (CHEMBL462605) is an approved small molecule (ATC N07XX11) targeting HRH1, HRH2, and HRH3; indicated across 10 conditions including narcolepsy and parkinson disease.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N07XX11
• Targets: 4 (HRH1, HRH2, HRH3…)
• Indications: 10 conditions
• Clinical trials: 32
• Chemistry: 295.8 Da · C17H26ClNO

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL462605
Name	Pitolisant
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	9948102
ATC	N07XX11
Molecular formula	C17H26ClNO
Molecular weight	295.8
InChIKey	NNACHAUCXXVJSP-UHFFFAOYSA-N

SMILES: C1CCN(CC1)CCCOCCCC2=CC=C(C=C2)Cl

IUPAC name: 1-[3-[3-(4-chlorophenyl)propoxy]propyl]piperidine

Also known as: BF-2.649, BF-2649, Bf2.649, BF2.649, HBS-101, Pitolisant, Tiprolisant, Wakix, europe, PITOLISANT, TIPROLISANT HYDROCHLORIDE, pitolisant

Parent form; salt/anhydrous children: CHEMBL4164059

Patent coverage: 164 distinct patent families (471 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
HRH1	H1 receptor	Antagonist	5.78	0%	P35367
HRH2	H2 receptor	Antagonist	4.96		P25021
HRH3	H3 receptor	Antagonist	8.57	0.5%	Q9Y5N1
HRH4	H4 receptor	Antagonist	4	0%	Q9H3N8

Broader ChEMBL bioactivity targets: 16 (assay-derived). Sample: Alpha-2C adrenergic receptor, Voltage-dependent L-type calcium channel subunit alpha-1C, Sodium channel protein type 5 subunit alpha, Muscarinic acetylcholine receptor M2, Sodium-dependent noradrenaline transporter, Sodium-dependent serotonin transporter, Histamine H1 receptor, Sodium-dependent dopamine transporter, Voltage-gated inwardly rectifying potassium channel KCNH2, Histamine H3 receptor.

Bioactivity

ChEMBL activities: 58 potent at pChembl ≥ 5 of 64 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
Q9JI35	9.8	Ki	0.16	nM	CHEMBL_ACT_19306700
HRH3	9.8	Ki	0.16	nM	CHEMBL_ACT_22795667
Q9JI35	9.8	Ki	0.16	nM	CHEMBL_ACT_2419852
HRH3	9.8	Ki	0.16	nM	CHEMBL_ACT_25500481
HRH3	9.8	Ki	0.16	nM	CHEMBL_ACT_2625431
HRH3	9.52	Ki	0.3	nM	CHEMBL_ACT_18423083
HRH3	9.52	Ki	0.3	nM	CHEMBL_ACT_18565511
HRH3	9.52	Ki	0.3	nM	CHEMBL_ACT_22913502
Q60492	9.3	Ki	0.5	nM	CHEMBL_ACT_25568859
HRH3	9.04	Ki	0.91	nM	CHEMBL_ACT_24504244
Q9JI35	8.82	EC50	1.5	nM	CHEMBL_ACT_2419851
HRH3	8.82	EC50	1.5	nM	CHEMBL_ACT_25500507
HRH3	8.81	Ki	1.55	nM	CHEMBL_ACT_25729317
HRH3	8.62	Ki	2.4	nM	CHEMBL_ACT_2419850
HRH3	8.6	Ki	2.51	nM	CHEMBL_ACT_24504290
HRH3	8.6	Ki	2.51	nM	CHEMBL_ACT_24516068
HRH3	8.6	Ki	2.51	nM	CHEMBL_ACT_25729336
HRH3	8.6	Ki	2.51	nM	CHEMBL_ACT_25729340
HRH3	8.6	Ki	2.51	nM	CHEMBL_ACT_2587802
HRH3	8.57	Ki	2.7	nM	CHEMBL_ACT_18289258
HRH3	8.57	Ki	2.7	nM	CHEMBL_ACT_2410698
HRH3	8.57	Ki	2.7	nM	CHEMBL_ACT_2419853
HRH3	8.57	Ki	2.7	nM	CHEMBL_ACT_3498234
HRH3	8.57	Ki	2.7	nM	CHEMBL_ACT_3514719
HRH3	8.57	Ki	2.7	nM	CHEMBL_ACT_6228045
HRH3	8.52	Ki	3	nM	CHEMBL_ACT_25105575
HRH3	8.43	Ki	3.71	nM	CHEMBL_ACT_25729357
Q9JI35	8.25	Kd	5.62	nM	CHEMBL_ACT_2419849
Q5U3Y7	8.19	Ki	6.5	nM	CHEMBL_ACT_25568902
HRH3	8.1	Ki	8	nM	CHEMBL_ACT_22472414

Target pathways

Aggregated over 4 target gene(s): HRH1, HRH2, HRH3, HRH4.

Top Reactome pathways

4 total, by targets touching each:

Pathway	Targets	Genes
Histamine receptors	4	HRH1, HRH2, HRH3, HRH4
G alpha (q) signalling events	1	HRH1
G alpha (s) signalling events	1	HRH2
G alpha (i) signalling events	1	HRH4

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	4
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	4
chemical synaptic transmission	4
signal transduction	4
inflammatory response	2
positive regulation of vasoconstriction	2
adenylate cyclase-activating G protein-coupled receptor signaling pathway	2
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway	2
phospholipase C-activating G protein-coupled receptor signaling pathway	1
memory	1
visual learning	1
regulation of vascular permeability	1
regulation of synaptic plasticity	1
cellular response to histamine	1
phospholipase C-activating serotonin receptor signaling pathway	1

Indications & clinical

Indications

10 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
narcolepsy	3	MONDO:0021107	MONDO:0021107
Parkinson disease	3	MONDO:0005180	MONDO:0005180
idiopathic hypersomnia	3	MONDO:0018044	MONDO:0018044
alcohol abuse	2	MONDO:0002046	MONDO:0007079
Prader-Willi syndrome	2	MONDO:0008300	MONDO:0008300
autism spectrum disorder	2	MONDO:0005258	EFO:0003756
drug dependence	1	MONDO:0005303	EFO:0003890
kidney disorder	1	MONDO:0005240	EFO:0003086

2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 32.

Phase distribution

Phase	Trials
PHASE3	18
PHASE2	6
PHASE1	5
Not specified	2
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05581576	PHASE4	UNKNOWN	Pitolisant in Refractory Restless Legs Syndrome
NCT06366464	PHASE3	RECRUITING	A Study of Pitolisant in Patients With Prader-Willi Syndrome
NCT07219485	PHASE3	ENROLLING_BY_INVITATION	A Study of Pitolisant in Participants With Prader-Willi Syndrome
NCT01036139	PHASE3	COMPLETED	Efficacy and Safety of BF2.649 in Excessive Daytime Sleepiness (EDS) in Parkinson’s Disease
NCT01066442	PHASE3	COMPLETED	Efficacy and Safety of BF2.649 in Excessive Daytime Sleepiness (EDS) in Parkinson’s Disease
NCT01067222	PHASE3	COMPLETED	Efficacy and Safety Study of BF2.649 in the Treatment of Excessive Daytime Sleepiness in Narcolepsy
NCT01067235	PHASE3	COMPLETED	Efficacy and Safety Study of BF2.649 and BF2.649 Add on Modafinil on Cataplexy in Patients With Narcolespy
NCT01071876	PHASE3	COMPLETED	BF2.649 in Patients With OSA and Treated by CPAP But Still Complaining of EDS
NCT01072968	PHASE3	COMPLETED	BF2.649 in Patients With OSA, Still Complaining of EDS and Refusing to be Treated by CPAP.
NCT01399606	PHASE3	COMPLETED	Long Term Open Label Study in Narcolepsy With BF2.649 (Pitolisant)
NCT01638403	PHASE3	COMPLETED	Effects of BF2.649 in the Treatment of Excessive Daytime Sleepiness in Narcolepsy.
NCT01789398	PHASE3	COMPLETED	Patient Narcoleptic Treated With BF2.649 (Pitolisant) in add-on to Sodium Oxybate (HARMONY IV)
NCT01800045	PHASE3	COMPLETED	Pitolisant to Assess Weekly Frequency of Cataplexy Attacks and EDS in Narcoleptic Patients (HARMONY CTP)
NCT02611687	PHASE3	COMPLETED	Efficacy and Safety of Pitolisant in Pediatric Narcoleptic Patients With or Without Cataplexy, Double-blind Study Followed by a Prolonged Open-label Period
NCT02739568	PHASE3	COMPLETED	Pitolisant (BF2.649) in the Treatment of EDS in Patients With OSA
NCT02978651	PHASE3	WITHDRAWN	Pitolisant (BF2.649) in the Treatment of Excessive Daytime Sleepiness in Patients With Obstructive Sleep Apnoea Syndrome, Treated or Not by Nasal Continuous Positive Airway Pressure, But Still Complaining of Excessive Daytime Sleepiness
NCT05156047	PHASE3	COMPLETED	A Phase 3 Study to Assess the Safety and Efficacy of Pitolisant in Adult Patients With Idiopathic Hypersomnia
NCT05223166	PHASE3	COMPLETED	A Clinical Study to Evaluate the Efficacy and Safety of Pitolisant in the Treatment of EDS in Patients With OSA
NCT05458128	PHASE3	COMPLETED	A Long-Term Safety and Effectiveness Study to Evaluate Pitolisant in Adult Patients With Idiopathic Hypersomnia
NCT05953389	PHASE2	ACTIVE_NOT_RECRUITING	Proof of Concept Study on Pitolisant Effect on Autism Spectrum Disorders in Children and Adolescents
NCT00690274	PHASE2	COMPLETED	Study to Demonstrate Cognitive Enhancing Effects of BF2.649
NCT01620554	PHASE2	COMPLETED	Dose-range Finding Study of BF2.649 Effect on Patients With Obstructive Sleep Apnea (OSA)
NCT02800083	PHASE2	WITHDRAWN	A Trial Evaluating Pitolisant (BF2.649) in Alcohol Use Disorder Treatment
NCT04257929	PHASE2	COMPLETED	A Phase 2 Study to Evaluate the Safety and Efficacy of Pitolisant in Patients With Prader-Willi Syndrome, Followed by an Open Label Extension
NCT04886518	PHASE2	COMPLETED	Safety and Efficacy of Pitolisant on Excessive Daytime Sleepiness and Other Non-Muscular Symptoms in Patients With Myotonic Dystrophy Type 1
NCT01619033	PHASE1	COMPLETED	Pharmacokinetics of BF2.649 in Renal Impairment
NCT02929342	PHASE1	COMPLETED	Study to Assess the Absorption, Distribution, Metabolism and Excretion (ADME) of [14C]-Pitolisant in Healthy Male Volunteers
NCT03152123	PHASE1	COMPLETED	Determination the Abuse Potential of Pitolisant in Healthy, Non-Dependent Recreational Stimulant Users
NCT04026750	PHASE1	TERMINATED	Insulin Tolerance Test Study in Patients With Type 1 Diabetes
NCT04596267	PHASE1	TERMINATED	Pitolisant Effects on Alcohol Self-Administration in Heavy Drinkers
NCT05536011	Not specified	RECRUITING	WAKIX® (Pitolisant) Pregnancy Registry
NCT03433131	Not specified	NO_LONGER_AVAILABLE	Expanded Access Program to Provide Treatment With Pitolisant to Adult Patients in the U.S. With Excessive Daytime Sleepiness Associated With Narcolepsy With or Without Cataplexy

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

477 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2, HRH3, HRH4
PIMOZIDE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2, HRH3, HRH4
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3, HRH4
HISTAMINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3, HRH4
GSK-1004723	ChEMBL	Phase 2	HRH1, HRH2, HRH3, HRH4
ACLIDINIUM BROMIDE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2, HRH3
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2, HRH4
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2, HRH3
Gefitinib	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2, HRH3
Linagliptin	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2, HRH3
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2, HRH4
Propoxyphene	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2, HRH3
RIFAMPIN	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2, HRH3
AMIODARONE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
CHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
CLEMASTINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
DEXCHLORPHENIRAMINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH4
DYCLONINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
FLUOXETINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
INDOCYANINE GREEN ACID FORM	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
IPRINDOLE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
KETOTIFEN	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH4
LOXAPINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH4
RISPERIDONE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
SULOCTIDIL	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
TETRACAINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
TRIFLUOPERAZINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2, HRH3
IMPROMIDINE	ChEMBL	Phase 2	HRH2, HRH3, HRH4
METERGOLINE	ChEMBL	Phase 2	HRH1, HRH2, HRH3
Afatinib	PubChem	Approved	HRH1, HRH2, HRH3
Alogliptin	PubChem	Approved	HRH1, HRH2, HRH3
Apixaban	PubChem	Approved	HRH1, HRH2, HRH3
Bosentan	PubChem	Approved	HRH1, HRH2, HRH3
Fidaxomicin	PubChem	Approved	HRH1, HRH2, HRH3
Fulvestrant	PubChem	Approved	HRH1, HRH2, HRH3
Pyrazinamide	PubChem	Approved	HRH1, HRH2, HRH3
saxagliptin	PubChem	Approved	HRH1, HRH2, HRH3
Tadalafil	PubChem	Approved	HRH1, HRH2, HRH3
Tafamidis	PubChem	Approved	HRH1, HRH2, HRH3
Tiotropium Bromide Monohydrate	PubChem	Approved	HRH1, HRH2, HRH3
CINACALCET	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2
Crizotinib	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2
ESCITALOPRAM	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2
Fedratinib	ChEMBL + PubChem	Phase 4 (approved)	HRH2, HRH3
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	HRH2, HRH3
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HRH2
Tegaserod	ChEMBL + PubChem	Phase 4 (approved)	HRH2, HRH3
ABEMACICLIB	ChEMBL	Phase 4 (approved)	HRH1, HRH3
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	HRH1, HRH3
AMISULPRIDE	ChEMBL	Phase 4 (approved)	HRH1, HRH3
AMOXAPINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2
ASENAPINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2
ATOMOXETINE	ChEMBL	Phase 4 (approved)	HRH1, HRH3
AZELASTINE	ChEMBL	Phase 4 (approved)	HRH1, HRH3
BENPERIDOL	ChEMBL	Phase 4 (approved)	HRH1, HRH3
BENZTROPINE	ChEMBL	Phase 4 (approved)	HRH1, HRH2