Lumateperone

Summary

Lumateperone (CHEMBL3306803) is an approved small molecule (ATC N05AD10) targeting DRD2, HTR2A, and SLC6A4; indicated across 5 conditions including psychotic disorder and major depressive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AD10
• Targets: 3 (DRD2, HTR2A, SLC6A4)
• Indications: 5 conditions
• Clinical trials: 26
• Chemistry: 393.5 Da · C24H28FN3O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3306803
Name	Lumateperone
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	21302490
ATC	N05AD10
Molecular formula	C24H28FN3O
Molecular weight	393.5
InChIKey	HOIIHACBCFLJET-SFTDATJTSA-N

SMILES: CN1CCN2[C@H]3CCN(C[C@H]3C4=C2C1=CC=C4)CCCC(=O)C5=CC=C(C=C5)F

IUPAC name: 1-(4-fluorophenyl)-4-[(10R,15S)-4-methyl-1,4,12-triazatetracyclo[7.6.1.05,16.010,15]hexadeca-5,7,9(16)-trien-12-yl]butan-1-one

Also known as: ITI 007, ITI-007, ITI-722, ITI007, Lumateperona, Lumateperone, LUMATEPERONE, lumateperone (Tosylate)

Parent form; salt/anhydrous children: CHEMBL3233142

Patent coverage: 287 distinct patent families (859 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 557 (65%) 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
DRD2	D2 receptor	Antagonist	7.49	0%	P14416
HTR2A	5-HT2A receptor	Antagonist	9.3	0%	P28223
SLC6A4	SERT	Inhibition	7.21	0.7%	P31645

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: D(2) dopamine receptor, 5-hydroxytryptamine receptor 2A, Sodium-dependent serotonin transporter.

Bioactivity

ChEMBL activities: 5 potent at pChembl ≥ 5 of 5 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2A	9.27	IC50	0.54	nM	CHEMBL_ACT_22795663
HTR2A	9.27	Ki	0.54	nM	CHEMBL_ACT_26186130
DRD2	8.49	IC50	3.2	nM	CHEMBL_ACT_22795666
SLC6A4	8.48	IC50	3.3	nM	CHEMBL_ACT_22795664
DRD2	8.39	IC50	4.1	nM	CHEMBL_ACT_22795665

Target pathways

Aggregated over 3 target gene(s): DRD2, HTR2A, SLC6A4.

Top Reactome pathways

14 total, by targets touching each:

Pathway	Targets	Genes
Neurotransmitter clearance	1	SLC6A4
Transmission across Chemical Synapses	1	SLC6A4
Neuronal System	1	SLC6A4
Signal Transduction	1	HTR2A
Signaling by GPCR	1	HTR2A
Class A/1 (Rhodopsin-like receptors)	1	HTR2A
Amine ligand-binding receptors	1	HTR2A
Serotonin clearance from the synaptic cleft	1	SLC6A4
GPCR downstream signalling	1	HTR2A
Dopamine receptors	1	DRD2
Serotonin receptors	1	HTR2A
G alpha (q) signalling events	1	HTR2A
SLC-mediated transport of neurotransmitters	1	SLC6A4
GPCR ligand binding	1	HTR2A

Dominant GO biological processes

GO term	Targets
response to xenobiotic stimulus	3
behavioral response to cocaine	3
temperature homeostasis	2
response to hypoxia	2
intracellular calcium ion homeostasis	2
response to toxic substance	2
regulation of dopamine secretion	2
response to estradiol	2
response to cocaine	2
release of sequestered calcium ion into cytosol	2
negative regulation of synaptic transmission, glutamatergic	2
positive regulation of ERK1 and ERK2 cascade	2
cellular response to retinoic acid	2
presynaptic modulation of chemical synaptic transmission	2
signal transduction	2

Indications & clinical

Indications

1 approved indication. FDA phase 4, plus an anticancer drug’s labelled cancer uses (which ChEMBL often logs at phase 3).

Indication	Phase	MONDO	EFO
psychotic disorder	4	MONDO:0005485	EFO:0005407

3 diseases in clinical trials (phase 1–3, investigational — not approved indications). Highest ChEMBL trial phase per disease; a non-cancer approved use is occasionally logged at phase 3 here.

Disease (in trials)	Phase	MONDO	EFO
major depressive disorder	3	MONDO:0002009	MONDO:0002009
bipolar disorder	3	MONDO:0004985	MONDO:0004985
Alzheimer disease	1	MONDO:0004975	MONDO:0004975

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

Clinical trials

Total trials: 26.

Phase distribution

Phase	Trials
PHASE3	17
PHASE4	3
PHASE2	3
PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06174116	PHASE4	RECRUITING	Metabolic Effects of Adjunctive Lumateperone Treatment in Clozapine-Treated Patients With Schizophrenia
NCT07369115	PHASE4	NOT_YET_RECRUITING	Neurocircuitry Mechanisms and Efficacy of Lumateperone as Adjunctive Therapy for Major Depressive Disorder and History of Early Life Abuse
NCT05890768	PHASE4	WITHDRAWN	Relationship Between Efficacy of Lumateperone and Brain Glutamate and Dopamine
NCT05850689	PHASE3	RECRUITING	Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder
NCT06372964	PHASE3	RECRUITING	Multicenter Study of Lumateperone for the Treatment of Bipolar Depression in Pediatric Patients
NCT06462586	PHASE3	RECRUITING	Study of Lumateperone in the Acute Treatment of Patients With Bipolar Mania
NCT06462612	PHASE3	RECRUITING	Study of Lumateperone in the Treatment of Patients With Bipolar Mania
NCT06482554	PHASE3	RECRUITING	Lumateperone for the Improvement of Apathy in Patients With Psychotic Symptoms.
NCT02282761	PHASE3	COMPLETED	A Trial to Assess the Antipsychotic Efficacy of ITI-007
NCT02469155	PHASE3	COMPLETED	A Trial to Assess the Antipsychotic Efficacy of ITI-007 Over 6 Weeks of Treatment
NCT02600494	PHASE3	COMPLETED	Clinical Trial Evaluating ITI-007 (Lumateperone) as a Monotherapy for the Treatment of Bipolar Depression
NCT02600507	PHASE3	COMPLETED	Clinical Trial Evaluating ITI-007 as an Adjunctive Therapy to Lithium or Valproate for the Treatment of Bipolar Depression
NCT02817906	PHASE3	TERMINATED	ITI-007 for the Treatment of Agitation in Patients With Dementia, Including Alzheimer’s Disease
NCT03249376	PHASE3	COMPLETED	Lumateperone Monotherapy for the Treatment of Bipolar Depression Conducted Globally
NCT04285515	PHASE3	COMPLETED	Clinical Trial Evaluating Lumateperone Monotherapy in the Treatment of Bipolar Depression or Major Depressive Disorder
NCT04959032	PHASE3	COMPLETED	Lumateperone for the Prevention of Relapse in Patients With Schizophrenia
NCT04985942	PHASE3	COMPLETED	Clinical Trial of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder
NCT05061706	PHASE3	COMPLETED	Multicenter Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder
NCT05061719	PHASE3	COMPLETED	An Open-label Study of Lumateperone as Adjunctive Therapy in the Treatment of Patients With Major Depressive Disorder
NCT01499563	PHASE2	COMPLETED	Study of a Novel Antipsychotic ITI-007 in Schizophrenia
NCT02078310	PHASE1/PHASE2	COMPLETED	Study of ITI-007 in Healthy Geriatric Volunteers and in Geriatric Patients With Dementia
NCT02288845	PHASE2	COMPLETED	Receptor Occupancy of ITI-007 Using Positron Emission Tomography (PET) in Patients With Stable Schizophrenia
NCT03817528	PHASE2	TERMINATED	ITI-007 (Lumateperone Tosylate) for Schizophrenia
NCT04779177	PHASE1	COMPLETED	Safety, Tolerability, and Pharmacokinetics of Lumateperone in Pediatric Patients With Schizophrenia or Schizoaffective Disorder
NCT06627413	PHASE1	COMPLETED	Safety, Tolerability, and Pharmacokinetics of Lumateperone Long-Acting Injectable Formulations in Patients With Schizophrenia or Schizoaffective Disorder

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.

690 molecules share ≥1 primary target. Top 100 by shared-target count:

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
Fidaxomicin	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
Propoxyphene	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
AMIODARONE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
AMOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
APOMORPHINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
ASENAPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
AZELASTINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
BENZTROPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
BEPRIDIL	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
BOSUTINIB	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
BROMPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CABERGOLINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CARIPRAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CARVEDILOL	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CINACALCET	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CINNARIZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CISAPRIDE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CLEMASTINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CLOZAPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
DARIFENACIN	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
DESIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
DESLORATADINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
DIBENZEPIN	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
DOBUTAMINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
DOMPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
DOTHIEPIN	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
DOXEPIN	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
DULOXETINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
EBASTINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
ECONAZOLE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
FLUOXETINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
HALOPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
ILOPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
IMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
KETANSERIN	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
LASOFOXIFENE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
LOFEPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
LOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
MEBEVERINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
MECLIZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
MIANSERIN	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
MICONAZOLE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
NAFTIFINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
NAFTOPIDIL	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
NEBIVOLOL	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
NEFAZODONE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
OLANZAPINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
OSIMERTINIB	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
PERPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
PIMOZIDE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
PIPAMAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
PIPERACETAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
PONATINIB	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
PRENYLAMINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
PROCHLORPERAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
PROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
PROMETHAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
QUINIDINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
RALOXIFENE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
RISPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
ROTIGOTINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
SALMETEROL	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
SERTINDOLE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
SERTRALINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
SULCONAZOLE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
SUNITINIB	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
TAMOXIFEN	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
TEGASEROD	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
TERFENADINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
THIETHYLPERAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
THIORIDAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
THIOTEPA	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
TIOCONAZOLE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
TRAZODONE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
TRIFLUOPERAZINE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
VERALIPRIDE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
VERAPAMIL	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	DRD2, HTR2A, SLC6A4
CINITAPRIDE	ChEMBL	Phase 3	DRD2, HTR2A, SLC6A4
MELITRACEN	ChEMBL	Phase 3	DRD2, HTR2A, SLC6A4
OPIPRAMOL	ChEMBL	Phase 3	DRD2, HTR2A, SLC6A4