Idalopirdine

Summary

Idalopirdine (CHEMBL3286580) is a phase-3 clinical-stage small molecule targeting HTR6 and HTR2C; indicated across 3 conditions including alzheimer disease.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (HTR6, HTR2C)
• Indications: 3 conditions
• Clinical trials: 9
• Chemistry: 398.4 Da · C20H19F5N2O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3286580
Name	Idalopirdine
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	21071390
Molecular formula	C20H19F5N2O
Molecular weight	398.4
InChIKey	YBAWYTYNMZWMMJ-UHFFFAOYSA-N

SMILES: C1=CC(=CC(=C1)OCC(C(F)F)(F)F)CNCCC2=CNC3=C2C=CC(=C3)F

IUPAC name: 2-(6-fluoro-1H-indol-3-yl)-N-[[3-(2,2,3,3-tetrafluoropropoxy)phenyl]methyl]ethanamine

Also known as: Idalopirdina, Idalopirdine, LU AE-58054, LU-AE-58054, Lu-ae58054, LU-AE58054, LY-483518, LY483518, Lu AE58054, SGS-518, SGS518, IDALOPIRDINE

Patent coverage: 125 distinct patent families (318 SureChEMBL compound mentions), from 3 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
HTR6	5-HT6 receptor	Antagonist	9.08	0.2%	P50406
HTR2C	5-HT2C receptor	Antagonist	6.6	0%	P28335

Broader ChEMBL bioactivity targets: 7 (assay-derived). Sample: 5-hydroxytryptamine receptor 1A, D(2) dopamine receptor, 5-hydroxytryptamine receptor 2A, 5-hydroxytryptamine receptor 2C, 5-hydroxytryptamine receptor 7, 5-hydroxytryptamine receptor 6, 5-hydroxytryptamine receptor 6.

Bioactivity

ChEMBL activities: 20 potent at pChembl ≥ 5 of 20 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR6	9.08	Ki	0.83	nM	CHEMBL_ACT_14723074
HTR6	9.08	Ki	0.83	nM	CHEMBL_ACT_14723128
HTR6	9.08	Ki	0.83	nM	CHEMBL_ACT_15035170
HTR6	9.08	Ki	0.83	nM	CHEMBL_ACT_18037961
HTR6	9.08	Ki	0.83	nM	CHEMBL_ACT_18383179
P31388	9.08	Ki	0.83	nM	CHEMBL_ACT_19406077
HTR6	9.08	Ki	0.83	nM	CHEMBL_ACT_24708971
HTR6	9.08	Ki	0.83	nM	CHEMBL_ACT_24742542
HTR6	9.08	Ki	0.83	nM	CHEMBL_ACT_24961703
HTR6	9.08	Ki	0.83	nM	CHEMBL_ACT_25083639
HTR6	8.45	Ki	3.54	nM	CHEMBL_ACT_18899289
HTR6	8.16	Ki	6.9	nM	CHEMBL_ACT_22916031
HTR6	7.58	IC50	26	nM	CHEMBL_ACT_24742558
HTR2C	6.6	Ki	250	nM	CHEMBL_ACT_14723070
HTR2C	6.6	Ki	251.2	nM	CHEMBL_ACT_14723124
HTR2A	6.1	Ki	791	nM	CHEMBL_ACT_18899308
HTR6	6	IC50	1000	nM	CHEMBL_ACT_22916042
DRD2	5.92	Ki	1215	nM	CHEMBL_ACT_18899364
HTR1A	5.41	Ki	3936	nM	CHEMBL_ACT_18899326
HTR7	5.06	Ki	8635	nM	CHEMBL_ACT_18899345

Target pathways

Aggregated over 2 target gene(s): HTR6, HTR2C.

Top Reactome pathways

9 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	2	HTR2C, HTR6
Signaling by GPCR	2	HTR2C, HTR6
Class A/1 (Rhodopsin-like receptors)	2	HTR2C, HTR6
Amine ligand-binding receptors	2	HTR2C, HTR6
GPCR downstream signalling	2	HTR2C, HTR6
Serotonin receptors	2	HTR2C, HTR6
GPCR ligand binding	2	HTR2C, HTR6
G alpha (q) signalling events	1	HTR2C
G alpha (s) signalling events	1	HTR6

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	2
chemical synaptic transmission	2
signal transduction	2
G protein-coupled receptor signaling pathway	2
G protein-coupled serotonin receptor signaling pathway	2
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase-activating serotonin receptor signaling pathway	1
cerebral cortex cell migration	1
positive regulation of TOR signaling	1
positive regulation of cell communication	1
positive regulation of signaling	1
behavioral fear response	1
intracellular calcium ion homeostasis	1
phospholipase C-activating G protein-coupled receptor signaling pathway	1
phospholipase C-activating serotonin receptor signaling pathway	1

Indications & clinical

Indications

3 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
Alzheimer disease	3	MONDO:0004975	MONDO:0004975

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

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
PHASE3	4
PHASE1	3
PHASE2	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01955161	PHASE3	COMPLETED	Study of Idalopirdine in Patients With Mild - Moderate Alzheimer’s Disease Treated With Donepezil
NCT02006641	PHASE3	COMPLETED	Idalopirdine in Patients With Mild-moderate Alzheimer’s Disease Treated With Donepezil
NCT02006654	PHASE3	COMPLETED	Study of Idalopirdine in Patients With Mild - Moderate Alzheimer’s Disease Treated With an Acetylcholinesterase Inhibitor
NCT02079246	PHASE3	COMPLETED	Long-term Safety and Tolerability of Idalopirdine (Lu AE58054) as Adjunctive Treatment to Donepezil in Patients With Mild-moderate Alzheimer’s Disease
NCT00810667	PHASE2	COMPLETED	Efficacy Study Exploring the Effect of Lu AE58054 as Augmentation Therapy in Patients With Schizophrenia
NCT01019421	PHASE2	COMPLETED	Lu AE58054 Added to Donepezil for the Treatment for Moderate Alzheimer’s Disease
NCT02019394	PHASE1	COMPLETED	Absolute Bioavailability of Lu AE58054 in Healthy Subjects
NCT02436486	PHASE1	COMPLETED	Study Investigating the Effect of Idalopirdine on Cardiac Repolarisation in Healthy Men
NCT03307993	PHASE1	TERMINATED	Positron Emission Tomography (PET) Study in Patients With Alzheimer’s Disease

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

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.

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

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HTR2C, HTR6
AMIODARONE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
AMLODIPINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
AMOXAPINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
ASENAPINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
AZELASTINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
BENZTROPINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
CARIPRAZINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
CARVEDILOL	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
CINACALCET	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
CLEMASTINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
CLOZAPINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
DESLORATADINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
DICYCLOMINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
DOXEPIN	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
EBASTINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
ECONAZOLE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
ERGOTAMINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
ESCITALOPRAM	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
FLUOXETINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
HALOPERIDOL	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
HALOPROGIN	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
ILOPERIDONE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
IMIPRAMINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
IPRINDOLE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
KETANSERIN	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
KETOTIFEN	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
LOXAPINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
MAPROTILINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
MEPAZINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
METHAPYRILENE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
METHYLERGONOVINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
METHYSERGIDE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
MIANSERIN	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
MICONAZOLE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
NEFAZODONE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
OLANZAPINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
ORPHENADRINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
OXYMETAZOLINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
PERGOLIDE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
PIMOZIDE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
PIPAMAZINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
PROCHLORPERAZINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
PROMAZINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
PROMETHAZINE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6
PROPAFENONE	ChEMBL	Phase 4 (approved)	HTR2C, HTR6