Sertindole

Summary

Sertindole (CHEMBL12713) is an approved small-molecule serotonergic antagonist (ATC N05AE03) targeting HTR1A, DRD2, and DRD3; indicated across 6 conditions including psychotic disorder and anxiety.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AE03
• Targets: 11 (HTR1A, DRD2, DRD3…)
• Indications: 6 conditions
• Clinical trials: 15
• Chemistry: 440.9 Da · C24H26ClFN4O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL12713
Name	Sertindole
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	60149
ChEBI	CHEBI:9122
ATC	N05AE03
Molecular formula	C24H26ClFN4O
Molecular weight	440.9
InChIKey	GZKLJWGUPQBVJQ-UHFFFAOYSA-N

SMILES: C1CN(CCC1C2=CN(C3=C2C=C(C=C3)Cl)C4=CC=C(C=C4)F)CCN5CCNC5=O

IUPAC name: 1-[2-[4-[5-chloro-1-(4-fluorophenyl)indol-3-yl]piperidin-1-yl]ethyl]imidazolidin-2-one

ChEBI definition: A phenylindole that is 1H-indole which is substituted on the nitrogen by a p-chlorophenyl group, at position 5 by chlorine, and at position 3 by a piperidin-4-yl group, which is itself substituted on the nitrogen by a 2-(2-oxoimidazolidin-1-yl)ethyl group.

Pharmacological roles (ChEBI): serotonergic antagonist, α-adrenergic antagonist, H1-receptor antagonist, second generation antipsychotic.

Also known as: Serdolect, Serlect, Sertindol, Sertindole, Zerdol, sertindole, SERTINDOLE, SID144206958, SID144206971, SID170465613

Patent coverage: 2,186 distinct patent families (8,984 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 8,938 (99%) 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
HTR1A	5-HT1A receptor	Antagonist	6.6	0%	P08908
DRD2	D2 receptor	Antagonist	8.92	0%	P14416
DRD3	D3 receptor	Antagonist	8.8	0%	P35462
DRD4	D4 receptor	Antagonist	9.07	0%	P21917
HRH1	H1 receptor	Antagonist	6.9	0%	P35367
HTR1B	5-HT1B receptor	Antagonist	7	0.2%	P28222
HTR1D	5-HT1D receptor	Antagonist	7.2	0%	P28221
HTR1E	5-ht1e receptor	Antagonist	6.4	0%	P28566
HTR1F	5-HT1F receptor	Antagonist	6.4	0.1%	P30939
HTR2A	5-HT2A receptor	Antagonist	9.4	0%	P28223
HTR2C	5-HT2C receptor	Inverse agonist	9.2	0%	P28335

Broader ChEMBL bioactivity targets: 50 (assay-derived). Sample: Vasopressin V2 receptor, 5-hydroxytryptamine receptor 2B, Neuronal acetylcholine receptor subunit alpha-4, 5-hydroxytryptamine receptor 1B, Adrenergic receptor alpha-1, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Amine oxidase [flavin-containing] A, Sodium channel protein type 5 subunit alpha, D(1A) dopamine receptor.

Bioactivity

ChEMBL activities: 87 potent at pChembl ≥ 5 of 99 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P14842	9.7	Ki	0.2	nM	CHEMBL_ACT_1206998
HTR2C	9.7	Ki	0.2	nM	CHEMBL_ACT_3507289
P18841	9.48	Ki	0.33	nM	CHEMBL_ACT_1206990
P18841	9.48	Ki	0.33	nM	CHEMBL_ACT_12651019
P18841	9.48	Ki	0.33	nM	CHEMBL_ACT_3506811
P18130	9.43	Ki	0.37	nM	CHEMBL_ACT_1206989
P18130	9.43	Ki	0.37	nM	CHEMBL_ACT_12651067
P18130	9.43	Ki	0.37	nM	CHEMBL_ACT_3506772
DRD2	9.42	Ki	0.38	nM	CHEMBL_ACT_25553904
P08909	9.41	IC50	0.39	nM	CHEMBL_ACT_1012212
P14842	9.41	IC50	0.39	nM	CHEMBL_ACT_1290228
P08909	9.41	IC50	0.39	nM	CHEMBL_ACT_151647
P08909	9.41	IC50	0.39	nM	CHEMBL_ACT_592132
P61169	9.35	Ki	0.45	nM	CHEMBL_ACT_1206993
DRD2	9.35	Ki	0.45	nM	CHEMBL_ACT_12651051
DRD2	9.35	Ki	0.45	nM	CHEMBL_ACT_3506889
P08909	9.32	IC50	0.48	nM	CHEMBL_ACT_1082832
P08909	9.29	Ki	0.51	nM	CHEMBL_ACT_1206999
HRH1	9.29	Ki	0.51	nM	CHEMBL_ACT_3507303
HTR2A	9.22	Ki	0.6	nM	CHEMBL_ACT_909007
P23944	9.18	Ki	0.66	nM	CHEMBL_ACT_1206991
P23944	9.18	Ki	0.66	nM	CHEMBL_ACT_12651014
P23944	9.18	Ki	0.66	nM	CHEMBL_ACT_3506850
HTR2A	9.07	Ki	0.85	nM	CHEMBL_ACT_464927
HTR2C	9	Ki	1	nM	CHEMBL_ACT_6231482
HTR2C	8.89	Ki	1.3	nM	CHEMBL_ACT_464928
P15823	8.85	Ki	1.4	nM	CHEMBL_ACT_1206988
ADRA1D	8.74	Ki	1.8	nM	CHEMBL_ACT_464929
DRD3	8.59	Ki	2.6	nM	CHEMBL_ACT_1206994
KCNH2	8.57	IC50	2.7	nM	CHEMBL_ACT_14741260

Target pathways

Aggregated over 11 target gene(s): HTR1A, DRD2, DRD3, DRD4, HRH1, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	7	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
Signaling by GPCR	7	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
Class A/1 (Rhodopsin-like receptors)	7	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
Amine ligand-binding receptors	7	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
Serotonin receptors	7	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
GPCR ligand binding	7	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
GPCR downstream signalling	6	HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
G alpha (i) signalling events	6	DRD3, DRD4, HTR1B, HTR1D, HTR1E, HTR1F
Dopamine receptors	3	DRD2, DRD3, DRD4
G alpha (q) signalling events	3	HRH1, HTR2A, HTR2C
Histamine receptors	1	HRH1

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	11
signal transduction	11
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	9
chemical synaptic transmission	9
adenylate cyclase-inhibiting serotonin receptor signaling pathway	5
intracellular calcium ion homeostasis	5
adenylate cyclase-activating G protein-coupled receptor signaling pathway	4
G protein-coupled serotonin receptor signaling pathway	4
behavioral response to cocaine	4
phospholipase C-activating serotonin receptor signaling pathway	4
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	4
behavioral fear response	3
serotonin receptor signaling pathway	3
adult behavior	3
regulation of behavior	3

Indications & clinical

Indications

6 indications (1 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
psychotic disorder	4	MONDO:0005485	EFO:0005407
anxiety	3	MONDO:0011918	EFO:0005230
dementia	3	MONDO:0001627	HP:0000726
depressive disorder	3	MONDO:0002050	MONDO:0002050

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

Clinical trials

Total trials: 15.

Phase distribution

Phase	Trials
PHASE3	6
Not specified	5
PHASE4	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00480844	PHASE4	UNKNOWN	Comparison of Cognitive Functions of Schizophrenic Patients Treated With Sertindole Versus Risperidone
NCT00763438	PHASE4	COMPLETED	Safety Study of an Antipsychotic, Sertindole, to Treat Schizophrenia
NCT02021201	PHASE4	TERMINATED	The Effect of Sertindole and Risperidone on Endophenotypic Markers of Schizophrenia
NCT02307396	PHASE4	COMPLETED	Evaluation of the Necessity of Long-term Pharmacological Treatment With Antipsychotics in Schizophrenic Patients
NCT00654706	PHASE3	COMPLETED	Efficacy Study Exploring the Effects on Cognition of Sertindole Versus Comparator in Patients With Schizophrenia
NCT00759421	PHASE3	COMPLETED	Exploratory Cognition Study of Sertindole in Patients With Schizophrenia
NCT00759460	PHASE3	COMPLETED	Study on Metabolic Parameters of Sertindole in Patients With Schizophrenia
NCT00856583	PHASE3	COMPLETED	Safety Study of Sertindole Versus Risperidone Under Normal Conditions of Use
NCT00864045	PHASE3	COMPLETED	Sertindole in Asian Patients With Schizophrenia
NCT02374567	PHASE3	TERMINATED	Pharmacovigilance in Gerontopsychiatric Patients
NCT00345982	Not specified	COMPLETED	Augmenting Clozapine With Sertindole - SERCLOZ
NCT00612079	Not specified	COMPLETED	The Effect of Sertindole on Sensory Gating and Cognition in Healthy Volunteers
NCT00629252	Not specified	TERMINATED	The Effect of Sertindole on Sensory Gating and Cognition in Schizophrenic Patients
NCT00885690	Not specified	TERMINATED	Comparing the Effects of Sertindole and Olanzapine on Cognition (SEROLA)
NCT01498770	Not specified	COMPLETED	An Observational Drug Utilization Study of Asenapine in the United Kingdom (P08308)

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.

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

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
RISPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1E, HTR1F, HTR2A, HTR2C
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1E, HTR1F, HTR2A, HTR2C
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1D, HTR1E, HTR2A, HTR2C
ERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
QUETIAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1E, HTR1F, HTR2A, HTR2C
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1D, HTR2A, HTR2C
CARIPRAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1D, HTR2A, HTR2C
KETANSERIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1D, HTR2A, HTR2C
NEFAZODONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1D, HTR2A, HTR2C
LYSERGIDE	ChEMBL	Phase 2	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1D, HTR1E, HTR2A, HTR2C
RITANSERIN	ChEMBL	Phase 2	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1E, HTR2A, HTR2C
ASENAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1E, HTR2A, HTR2C
CYPROHEPTADINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, HRH1, HTR1A, HTR1E, HTR1F, HTR2A, HTR2C
METHYLERGONOVINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, HRH1, HTR1A, HTR1E, HTR1F, HTR2A, HTR2C
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1B, HTR1D, HTR2A, HTR2C
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1E, HTR2A
RIZATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
ZIPRASIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1E, HTR2A, HTR2C
AZELASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1, HTR1B, HTR1D, HTR1E, HTR2A, HTR2C
MIANSERIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1D, HTR2A, HTR2C
SALMETEROL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HTR1A, HTR1B, HTR1D, HTR2A, HTR2C
SEROTONIN	ChEMBL + PubChem	Phase 3 (approved)	DRD3, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
YOHIMBINE	ChEMBL + PubChem	Phase 3 (approved)	DRD2, DRD3, HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A
PENFLURIDOL	ChEMBL	Phase 2	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1D, HTR2A, HTR2C
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
Fidaxomicin	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
Propoxyphene	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
SUMATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR1F, HTR2A, HTR2C
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
AMOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
APOMORPHINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
BENPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
CINACALCET	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1, HTR1A, HTR1D, HTR2A, HTR2C
DOXEPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
EBASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
HALOPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
ILOPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
IPRINDOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
LOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
PERGOLIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
PIMOZIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
PROCHLORPERAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
PROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
PROMETHAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
SILODOSIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1D
SUNITINIB	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
TEGASEROD	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HTR1A, HTR1D, HTR2A, HTR2C
THIORIDAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
THIOTHIXENE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
TRAZODONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C
VILAZODONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR1B, HTR1D
XYLOMETAZOLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HTR1A, HTR1B, HTR1D, HTR2A, HTR2C
LATREPIRDINE	ChEMBL	Phase 3	DRD2, DRD3, HRH1, HTR1D, HTR1E, HTR2A, HTR2C
LISURIDE	ChEMBL	Phase 3	DRD2, DRD3, DRD4, HRH1, HTR1A, HTR2A, HTR2C