Iloperidone

Summary

Iloperidone (CHEMBL14376) is an approved small-molecule serotonergic antagonist (ATC N05AX14) targeting HTR6, HTR7, and HTR1A; indicated across 5 conditions including psychotic disorder and bipolar disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AX14
• Targets: 4 (HTR6, HTR7, HTR1A…)
• Indications: 5 conditions
• Clinical trials: 24
• Chemistry: 426.5 Da · C24H27FN2O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL14376
Name	Iloperidone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	71360
ChEBI	CHEBI:65173
ATC	N05AX14
Molecular formula	C24H27FN2O4
Molecular weight	426.5
InChIKey	XMXHEBAFVSFQEX-UHFFFAOYSA-N

SMILES: CC(=O)C1=CC(=C(C=C1)OCCCN2CCC(CC2)C3=NOC4=C3C=CC(=C4)F)OC

IUPAC name: 1-[4-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy]-3-methoxyphenyl]ethanone

ChEBI definition: A member of the class of piperidines that is the 4-acetyl-2-methoxyphenyl ether of 3-(piperidin-1-yl)propan-1-ol which is substituted at position 4 of the piperidine ring by a 6-fluoro-1,2-benzoxazol-3-yl group. A member of the group of second generation antipsychotics (also known as an atypical antipsychotics), it is used for the treatment of schizophrenia.

Pharmacological roles (ChEBI): serotonergic antagonist, dopaminergic antagonist, second generation antipsychotic.

Also known as: Fanapt, HP 873, HP-873, Iloperidona, Iloperidone, ILOPERIDONE, SID144207159, SID170465198, SID124899318, ILOPERIDONE (FANAPT), Iloperidone (Fanapt), iloperidone

Patent coverage: 2,035 distinct patent families (7,878 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 7,735 (98%) 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	7.2	0.2%	P50406
HTR7	5-HT7 receptor	Antagonist	7	0.8%	P34969
HTR1A	5-HT1A receptor	Antagonist	7	0%	P08908
DRD2	D2 receptor	Antagonist	6.96	0%	P14416

Broader ChEMBL bioactivity targets: 34 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Neuronal acetylcholine receptor subunit alpha-4, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, D(1A) dopamine receptor, Serotonin 2 (5-HT2) receptor, Muscarinic acetylcholine receptor M2, 5-hydroxytryptamine receptor 1A, Muscarinic acetylcholine receptor M1.

Bioactivity

ChEMBL activities: 45 potent at pChembl ≥ 5 of 50 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2A	9.52	AC50	0.3	nM	CHEMBL_ACT_25173743
P22909	9.4	IC50	0.4	nM	CHEMBL_ACT_640444
ADRA1A	8.74	AC50	1.8	nM	CHEMBL_ACT_25138498
ADRA1A	8.52	AC50	3	nM	CHEMBL_ACT_25219208
HTR2A	8.51	AC50	3.1	nM	CHEMBL_ACT_25225543
P08909	8.05	IC50	9	nM	CHEMBL_ACT_640431
Q75Z89	8.05	IC50	9	nM	CHEMBL_ACT_640445
ADRA1A	8.04	AC50	9.2	nM	CHEMBL_ACT_25218370
DRD1	8	AC50	10	nM	CHEMBL_ACT_25115630
DRD3	8	AC50	9.9	nM	CHEMBL_ACT_25194931
ADRA2C	7.75	AC50	18	nM	CHEMBL_ACT_25148292
DRD4	7.68	AC50	20.9	nM	CHEMBL_ACT_25127456
DRD3	7.43	AC50	37.3	nM	CHEMBL_ACT_25193931
HRH1	7.35	AC50	44.7	nM	CHEMBL_ACT_25212924
DRD2	7.34	AC50	45.4	nM	CHEMBL_ACT_25140746
HTR1A	7.26	AC50	55	nM	CHEMBL_ACT_25216295
ADRA2A	7.22	AC50	60	nM	CHEMBL_ACT_25156849
SIGMAR1	7.19	IC50	64	nM	CHEMBL_ACT_640449
DRD1	7.17	AC50	68.4	nM	CHEMBL_ACT_25114831
HTR1A	7.11	AC50	78.5	nM	CHEMBL_ACT_25164623
ADRA2B	6.98	AC50	105.5	nM	CHEMBL_ACT_25144101
HTR1A	6.96	AC50	110	nM	CHEMBL_ACT_25165444
P61169	6.96	IC50	110	nM	CHEMBL_ACT_640430
DRD2	6.96	IC50	110	nM	CHEMBL_ACT_640447
KCNH2	6.82	AC50	150	nM	CHEMBL_ACT_25118450
ADRA2A	6.75	AC50	175.8	nM	CHEMBL_ACT_25156044
Q64264	6.68	IC50	210	nM	CHEMBL_ACT_640446
HTR6	6.59	AC50	257	nM	CHEMBL_ACT_25119002
SLC6A4	6.54	AC50	290	nM	CHEMBL_ACT_25151747
SLC6A4	6.44	AC50	360	nM	CHEMBL_ACT_25150728

Target pathways

Aggregated over 4 target gene(s): HTR6, HTR7, HTR1A, DRD2.

Top Reactome pathways

10 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	3	HTR1A, HTR6, HTR7
Signaling by GPCR	3	HTR1A, HTR6, HTR7
Class A/1 (Rhodopsin-like receptors)	3	HTR1A, HTR6, HTR7
Amine ligand-binding receptors	3	HTR1A, HTR6, HTR7
Serotonin receptors	3	HTR1A, HTR6, HTR7
GPCR ligand binding	3	HTR1A, HTR6, HTR7
GPCR downstream signalling	2	HTR6, HTR7
G alpha (s) signalling events	2	HTR6, HTR7
Dopamine receptors	1	DRD2
RHOBTB3 ATPase cycle	1	HTR7

Dominant GO biological processes

GO term	Targets
signal transduction	4
G protein-coupled receptor signaling pathway	4
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	3
chemical synaptic transmission	3
G protein-coupled serotonin receptor signaling pathway	3
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	2
adenylate cyclase-activating serotonin receptor signaling pathway	2
adult behavior	2
cerebral cortex cell migration	1
positive regulation of TOR signaling	1
positive regulation of cell communication	1
positive regulation of signaling	1
smooth muscle contraction	1
circadian rhythm	1
blood circulation	1

Indications & clinical

Indications

5 indications (2 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
bipolar disorder	3	MONDO:0004985	EFO:0009963
post-traumatic stress disorder	2	MONDO:0005146	EFO:0001358
liver disorder	1	MONDO:0005154	EFO:0001421

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

Clinical trials

Total trials: 24.

Phase distribution

Phase	Trials
PHASE4	6
PHASE1	6
PHASE3	5
PHASE2	4
Not specified	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05648591	PHASE4	RECRUITING	Safety and Tolerability of Open-Labeled Iloperidone in Adolescents
NCT01207414	PHASE4	COMPLETED	Switching to Iloperidone From Other Antipsychotics in Schizophrenia
NCT01464229	PHASE4	COMPLETED	Iloperidone Augmentation of SSRIs for Patients With Major Depressive Disorder With Residual Anger and Irritability
NCT01920802	PHASE4	COMPLETED	Assessment and Comparison of Metabolic Changes in Non-psychotic Adults Taking Iloperidone or Olanzapine or Placebo
NCT01929889	PHASE4	TERMINATED	Assessing the Effects of Fanapt® on Social Cognition in Schizophrenia
NCT02413918	PHASE4	COMPLETED	Iloperidone in Mixed States of Bipolar Disorder
NCT06961968	PHASE3	RECRUITING	Randomized Withdrawal Study in Patients With Schizophrenia
NCT00254202	PHASE3	COMPLETED	Efficacy and Safety of Iloperidone Compared With Placebo and Active Control in Subjects With Acute Schizophrenia
NCT01291511	PHASE3	COMPLETED	Relapse Prevention Study in Patients With Schizophrenia
NCT02453893	PHASE3	UNKNOWN	Risperidone-controlled,Multicentre Clinical Trial of Iloperidone in Patients With Schizophrenia
NCT04819776	PHASE3	COMPLETED	Evaluation of Efficacy and Safety of Iloperidone in the Acute Treatment of Manic or Mixed Episodes Associated With Bipolar I Disorder
NCT07090161	PHASE2	RECRUITING	Evaluation of Efficacy and Safety of Iloperidone for the Treatment of Participants With Uncontrolled Hypertension
NCT01348100	PHASE1/PHASE2	COMPLETED	Safety, Tolerability, and Pharmacokinetics of Iloperidone Depot in Schizophrenic Patients
NCT01623713	PHASE2	COMPLETED	Efficacy and Safety Study of Iloperidone Virus Risperidone to Treat Schizophrenia
NCT01917318	PHASE2	TERMINATED	Iloperidone for Symptoms of Arousal in Post Traumatic Stress Disorder (PTSD)
NCT05344365	PHASE2	WITHDRAWN	A Study to Evaluate Iloperidone for the Treatment of Parkinson’s Disease Psychosis
NCT01529294	PHASE1	COMPLETED	Single-dose Iloperidone Pharmacokinetics in Patients With Mild or Moderate Liver Disease, Compared to Healthy Volunteers
NCT03420534	PHASE1	UNKNOWN	Human Bioequivalence Test (Fasting & Postprandial) of Iloperidone Tablets
NCT04127058	PHASE1	COMPLETED	Evaluating a New Iloperidone Titration Scheme in Bipolar I Disorder or Schizophrenia
NCT04712734	PHASE1	COMPLETED	A Study to Evaluate Iloperidone Long-acting Injection (LAI) for the Treatment of Schizophrenia
NCT04969211	PHASE1	COMPLETED	Bioequivalence Study Between VHX-896 Tablets and Iloperidone Tablets in Healthy Volunteers
NCT06494397	PHASE1	COMPLETED	Pharmacokinetic Study of VHX-896 and Iloperidone Tablets Under Steady-State Conditions
NCT01498770	Not specified	COMPLETED	An Observational Drug Utilization Study of Asenapine in the United Kingdom (P08308)
NCT02600741	Not specified	COMPLETED	Family Intervention in Recent Onset Schizophrenia Treatment (FIRST)

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 5 clinical and 9 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

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

Molecule	Source	Status	Shared targets
BREXPIPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
AMOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
CARIPRAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
CARVEDILOL	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
CINACALCET	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
CLOZAPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
DIBENZEPIN	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
DOXEPIN	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
HALOPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
IMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
KETANSERIN	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
LOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
METHYSERGIDE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
MIANSERIN	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
NEFAZODONE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
OLANZAPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
PROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
QUETIAPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
RISPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
TEGASEROD	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
THIORIDAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
THIOTHIXENE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
VILAZODONE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6, HTR7
BRILAROXAZINE	ChEMBL	Phase 3	DRD2, HTR1A, HTR6, HTR7
IDALOPIRDINE	ChEMBL	Phase 3	DRD2, HTR1A, HTR6, HTR7
INTEPIRDINE	ChEMBL	Phase 3	DRD2, HTR1A, HTR6, HTR7
FANANSERIN	ChEMBL	Phase 2	DRD2, HTR1A, HTR6, HTR7
IPSAPIRONE	ChEMBL	Phase 2	DRD2, HTR1A, HTR6, HTR7
LYSERGIDE	ChEMBL	Phase 2	DRD2, HTR1A, HTR6, HTR7
METERGOLINE	ChEMBL	Phase 2	DRD2, HTR1A, HTR6, HTR7
NIGULDIPINE	ChEMBL	Phase 2	DRD2, HTR1A, HTR6, HTR7
PENFLURIDOL	ChEMBL	Phase 2	DRD2, HTR1A, HTR6, HTR7
RITANSERIN	ChEMBL	Phase 2	DRD2, HTR1A, HTR6, HTR7
SPIPERONE	ChEMBL	Phase 2	DRD2, HTR1A, HTR6, HTR7
SPIRAMIDE	ChEMBL	Phase 2	DRD2, HTR1A, HTR6, HTR7
Pyrazinamide	PubChem	Approved	DRD2, HTR1A, HTR6, HTR7
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HTR1A, HTR7
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6
AMLODIPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6
ASENAPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6
AZELASTINE	ChEMBL	Phase 4 (approved)	DRD2, HTR6, HTR7
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6
BUSPIRONE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR7
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6
CISAPRIDE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR7
CLEMASTINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6
DESLORATADINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6
DISULFIRAM	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6
EBASTINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6
ERGOTAMINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR6
FROVATRIPTAN	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR7
HYDROXYZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR6, HTR7