Intepirdine

Summary

Intepirdine (CHEMBL1083390) is a phase-3 clinical-stage small molecule targeting HTR6; indicated across 2 conditions including alzheimer disease and dementia.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (HTR6)
• Indications: 2 conditions
• Clinical trials: 9
• Chemistry: 353.4 Da · C19H19N3O2S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1083390
Name	Intepirdine
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	11256720
Molecular formula	C19H19N3O2S
Molecular weight	353.4
InChIKey	JJZFWROHYSMCMU-UHFFFAOYSA-N

SMILES: C1CN(CCN1)C2=CC=CC3=CC(=CN=C32)S(=O)(=O)C4=CC=CC=C4

IUPAC name: 3-(benzenesulfonyl)-8-piperazin-1-ylquinoline

Also known as: GSK-742457, GSK742457, Intepirdina, Intepirdine, RVT-101, Sb-742457, SB-742457, INTEPIRDINE, IntepirdineÊ, IntepirdineÂ, Interpirdine

Patent coverage: 122 distinct patent families (320 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 215 (67%) of the total. 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	9.77	0.2%	P50406

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

Bioactivity

ChEMBL activities: 27 potent at pChembl ≥ 5 of 29 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR6	9.78	Ki	0.17	nM	CHEMBL_ACT_14723140
HTR6	9.77	Ki	0.17	nM	CHEMBL_ACT_14723088
HTR6	9.77	Ki	0.17	nM	CHEMBL_ACT_25519692
HTR6	9.64	Ki	0.23	nM	CHEMBL_ACT_13398106
HTR6	9.64	Ki	0.23	nM	CHEMBL_ACT_18037962
P31388	9.63	Ki	0.23	nM	CHEMBL_ACT_19406078
HTR6	9.63	Ki	0.23	nM	CHEMBL_ACT_3302095
HTR6	9.6	Ki	0.25	nM	CHEMBL_ACT_15035190
HTR6	9.6	Ki	0.25	nM	CHEMBL_ACT_24961704
HTR6	9.55	Ki	0.28	nM	CHEMBL_ACT_18383180
HTR6	8.89	Ki	1.3	nM	CHEMBL_ACT_26039968
HTR6	8.85	Ki	1.4	nM	CHEMBL_ACT_18299114
HTR6	8.85	Ki	1.4	nM	CHEMBL_ACT_18383126
HTR6	8.85	Ki	1.4	nM	CHEMBL_ACT_22918991
HTR6	8.85	Ki	1.4	nM	CHEMBL_ACT_23313177
HTR6	8.85	Ki	1.4	nM	CHEMBL_ACT_25659789
HTR6	8.55	IC50	2.8	nM	CHEMBL_ACT_18383131
HTR6	8.55	IC50	2.8	nM	CHEMBL_ACT_22919002
HTR6	8.55	IC50	2.8	nM	CHEMBL_ACT_23313261
HTR2A	7.6	Ki	25.1	nM	CHEMBL_ACT_26039981
HTR2A	7.58	Ki	26	nM	CHEMBL_ACT_18383141
HTR1A	7.58	Ki	26	nM	CHEMBL_ACT_22919020
HTR6	7.01	IC50	97	nM	CHEMBL_ACT_22798793
DRD2	6	Ki	997	nM	CHEMBL_ACT_18383151
DRD2	6	Ki	997	nM	CHEMBL_ACT_22919032
HTR1A	5.62	Ki	2370	nM	CHEMBL_ACT_18383136
HTR1A	5.62	Ki	2370	nM	CHEMBL_ACT_22919014

Target pathways

Aggregated over 1 target gene(s): HTR6.

Top Reactome pathways

8 total, by targets touching each:

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

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase-activating serotonin receptor signaling pathway	1
chemical synaptic transmission	1
cerebral cortex cell migration	1
positive regulation of TOR signaling	1
signal transduction	1
G protein-coupled receptor signaling pathway	1
positive regulation of cell communication	1
positive regulation of signaling	1
G protein-coupled serotonin receptor signaling pathway	1

Indications & clinical

Indications

2 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
dementia	2	MONDO:0001627	HP:0000726

Clinical trials

Total trials: 9.

Phase distribution

Phase	Trials
PHASE2	6
PHASE3	1
PHASE2/PHASE3	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02585934	PHASE3	COMPLETED	Study Evaluating Intepirdine (RVT-101) in Subjects With Mild to Moderate Alzheimer’s Disease on Donepezil: MINDSET Study
NCT02928445	PHASE2/PHASE3	TERMINATED	Long-Term Extension Study of Intepirdine (RVT-101) in Subjects With Dementia With Lewy Bodies: HEADWAY-DLB Extension
NCT00224497	PHASE2	COMPLETED	A Dose Ranging Study To Investigate The Efficacy And Safety Of SB-742457 In Alzheimer’s Disease
NCT00348192	PHASE2	COMPLETED	SB-742457 And Donepezil In Alzheimer’s Disease
NCT00708552	PHASE2	COMPLETED	Study of SB-742457 or Donepezil Versus Placebo in Subjects With Mild-to-moderate Alzheimer’s Disease
NCT00710684	PHASE2	COMPLETED	A Study of SB-742457, Added to Donepezil for the Treatment of Mild-to-moderate Alzheimer’s Disease
NCT02669433	PHASE2	COMPLETED	Study Evaluating Intepirdine (RVT-101) in Subjects With Dementia With Lewy Bodies: The HEADWAY-DLB Study
NCT02910102	PHASE2	COMPLETED	Study Evaluating Intepirdine (RVT-101) on Gait and Balance in Subjects With Dementia
NCT00551772	PHASE1	COMPLETED	A Study To Assess The Pharmacokinetics Of SB-742457 Formulated As A Capsule And A Tablet In Healthy Elderly Volunteers.

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.

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

Molecule	Source	Status	Shared targets
AMIODARONE	ChEMBL	Phase 4 (approved)	HTR6
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	HTR6
AMLODIPINE	ChEMBL	Phase 4 (approved)	HTR6
AMOXAPINE	ChEMBL	Phase 4 (approved)	HTR6
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR6
ASENAPINE	ChEMBL	Phase 4 (approved)	HTR6
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	HTR6
AZELASTINE	ChEMBL	Phase 4 (approved)	HTR6
BELINOSTAT	ChEMBL	Phase 4 (approved)	HTR6
BENZTROPINE	ChEMBL	Phase 4 (approved)	HTR6
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	HTR6
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	HTR6
CARIPRAZINE	ChEMBL	Phase 4 (approved)	HTR6
CARVEDILOL	ChEMBL	Phase 4 (approved)	HTR6
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	HTR6
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	HTR6
CINACALCET	ChEMBL	Phase 4 (approved)	HTR6
CLEMASTINE	ChEMBL	Phase 4 (approved)	HTR6
CLOMIPHENE	ChEMBL	Phase 4 (approved)	HTR6
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	HTR6
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	HTR6
CLOZAPINE	ChEMBL	Phase 4 (approved)	HTR6
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	HTR6
DAPSONE	ChEMBL	Phase 4 (approved)	HTR6
DESLORATADINE	ChEMBL	Phase 4 (approved)	HTR6
DIBENZEPIN	ChEMBL	Phase 4 (approved)	HTR6
DICYCLOMINE	ChEMBL	Phase 4 (approved)	HTR6
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	HTR6
DIHYDROERGOTAMINE	ChEMBL	Phase 4 (approved)	HTR6
DIPHENHYDRAMINE	ChEMBL	Phase 4 (approved)	HTR6
DISULFIRAM	ChEMBL	Phase 4 (approved)	HTR6
DOXEPIN	ChEMBL	Phase 4 (approved)	HTR6
EBASTINE	ChEMBL	Phase 4 (approved)	HTR6
ECONAZOLE	ChEMBL	Phase 4 (approved)	HTR6
ERGOTAMINE	ChEMBL	Phase 4 (approved)	HTR6
ESCITALOPRAM	ChEMBL	Phase 4 (approved)	HTR6
FLUOXETINE	ChEMBL	Phase 4 (approved)	HTR6
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	HTR6
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	HTR6
FLUTAMIDE	ChEMBL	Phase 4 (approved)	HTR6
HALOPERIDOL	ChEMBL	Phase 4 (approved)	HTR6
HALOPROGIN	ChEMBL	Phase 4 (approved)	HTR6
HYDROXYZINE	ChEMBL	Phase 4 (approved)	HTR6
ILOPERIDONE	ChEMBL	Phase 4 (approved)	HTR6
IMIPRAMINE	ChEMBL	Phase 4 (approved)	HTR6
IPRINDOLE	ChEMBL	Phase 4 (approved)	HTR6
KETANSERIN	ChEMBL	Phase 4 (approved)	HTR6
KETOTIFEN	ChEMBL	Phase 4 (approved)	HTR6
LOXAPINE	ChEMBL	Phase 4 (approved)	HTR6
MAPROTILINE	ChEMBL	Phase 4 (approved)	HTR6
MEPAZINE	ChEMBL	Phase 4 (approved)	HTR6
METHAPYRILENE	ChEMBL	Phase 4 (approved)	HTR6
METHYLERGONOVINE	ChEMBL	Phase 4 (approved)	HTR6
METHYSERGIDE	ChEMBL	Phase 4 (approved)	HTR6
MIANSERIN	ChEMBL	Phase 4 (approved)	HTR6
MICONAZOLE	ChEMBL	Phase 4 (approved)	HTR6
MITOTANE	ChEMBL	Phase 4 (approved)	HTR6
NEFAZODONE	ChEMBL	Phase 4 (approved)	HTR6
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	HTR6
OLANZAPINE	ChEMBL	Phase 4 (approved)	HTR6