Cariprazine

Summary

Cariprazine (CHEMBL2028019) is an approved small-molecule dopamine agonist (ATC N05AX15) targeting DRD2 and DRD3; indicated across 8 conditions including psychotic disorder and major depressive disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AX15
• Targets: 2 (DRD2, DRD3)
• Indications: 8 conditions
• Clinical trials: 46
• Chemistry: 427.4 Da · C21H32Cl2N4O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2028019
Name	Cariprazine
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	11154555
ChEBI	CHEBI:90933
ATC	N05AX15
Molecular formula	C21H32Cl2N4O
Molecular weight	427.4
InChIKey	KPWSJANDNDDRMB-UHFFFAOYSA-N

SMILES: CN(C)C(=O)NC1CCC(CC1)CCN2CCN(CC2)C3=C(C(=CC=C3)Cl)Cl

IUPAC name: 3-[4-[2-[4-(2,3-dichlorophenyl)piperazin-1-yl]ethyl]cyclohexyl]-1,1-dimethylurea

ChEBI definition: An N-alkylpiperazine that is N,N-dimethyl-N’-{trans-4-[2-(piperazin-1-yl)ethyl]cyclohexyl}urea substituted at position 4 on the piperazine ring by a 2,3-dichlorophenyl group. Used (as the hydrochloride salt) for treatment of schizophrenia and bipolar disorder.

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

Also known as: Cariprazina, Cariprazine, Fri-7000188, GED-129, MP-214, Reagila, RGH-188, CARIPRAZINE, cariprazine

Parent form; salt/anhydrous children: CHEMBL2024517

Patent coverage: 632 distinct patent families (1,576 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 1,544 (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
DRD2	D2 receptor	Partial agonist	8.24	0%	P14416
DRD3	D3 receptor	Partial agonist	10.05	0%	P35462

Broader ChEMBL bioactivity targets: 19 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, D(1B) dopamine receptor, Alpha-2A adrenergic receptor, Adrenergic receptor alpha-1, D(1A) dopamine receptor, Muscarinic acetylcholine receptor M2, 5-hydroxytryptamine receptor 1A, Muscarinic acetylcholine receptor M1, D(2) dopamine receptor, D(4) dopamine receptor.

Bioactivity

ChEMBL activities: 89 potent at pChembl ≥ 5 of 91 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
DRD3	10.07	Ki	0.09	nM	CHEMBL_ACT_18057401
DRD3	10.07	Ki	0.09	nM	CHEMBL_ACT_22435650
DRD3	10.07	Ki	0.09	nM	CHEMBL_ACT_25011693
DRD3	10.02	Ki	0.1	nM	CHEMBL_ACT_16819806
HTR2B	9.82	Ki	0.15	nM	CHEMBL_ACT_25686102
DRD2	9.74	EC50	0.18	nM	CHEMBL_ACT_25011703
DRD3	9.66	Ki	0.22	nM	CHEMBL_ACT_25685859
DRD3	9.57	Ki	0.27	nM	CHEMBL_ACT_14732018
DRD3	9.57	Ki	0.27	nM	CHEMBL_ACT_18252366
DRD3	9.57	Ki	0.27	nM	CHEMBL_ACT_23301647
DRD3	9.57	Ki	0.27	nM	CHEMBL_ACT_23301648
DRD2	9.4	EC50	0.4	nM	CHEMBL_ACT_19218367
DRD2	9.39	Ki	0.41	nM	CHEMBL_ACT_14731997
DRD2	9.39	Ki	0.41	nM	CHEMBL_ACT_18252360
DRD2	9.35	EC50	0.45	nM	CHEMBL_ACT_19218550
DRD2	9.33	Ki	0.47	nM	CHEMBL_ACT_14731976
DRD2	9.33	Ki	0.47	nM	CHEMBL_ACT_18252354
DRD2	9.31	Ki	0.49	nM	CHEMBL_ACT_18057402
DRD2	9.31	Ki	0.49	nM	CHEMBL_ACT_18891558
DRD2	9.31	Ki	0.49	nM	CHEMBL_ACT_22435675
DRD2	9.3	Ki	0.5	nM	CHEMBL_ACT_24842599
DRD2	9.22	EC50	0.6	nM	CHEMBL_ACT_19218458
DRD2	9.2	EC50	0.63	nM	CHEMBL_ACT_19218581
DRD2	9.16	Ki	0.69	nM	CHEMBL_ACT_18057403
DRD2	9.11	Ki	0.78	nM	CHEMBL_ACT_25685824
DRD2	8.99	EC50	1.02	nM	CHEMBL_ACT_23301383
DRD2	8.99	EC50	1.02	nM	CHEMBL_ACT_23301384
DRD2	8.89	Ki	1.3	nM	CHEMBL_ACT_16819844
DRD2	8.87	EC50	1.35	nM	CHEMBL_ACT_25685954
DRD2	8.87	EC50	1.35	nM	CHEMBL_ACT_25685969

Target pathways

Aggregated over 2 target gene(s): DRD2, DRD3.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Dopamine receptors	2	DRD2, DRD3
G alpha (i) signalling events	1	DRD3

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor internalization	2
intracellular calcium ion homeostasis	2
adenylate cyclase-inhibiting dopamine receptor signaling pathway	2
locomotory behavior	2
visual learning	2
response to xenobiotic stimulus	2
regulation of dopamine secretion	2
positive regulation of cytokinesis	2
circadian regulation of gene expression	2
response to histamine	2
response to cocaine	2
dopamine metabolic process	2
regulation of potassium ion transport	2
response to morphine	2
negative regulation of blood pressure	2

Indications & clinical

Indications

8 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
major depressive disorder	3	MONDO:0002009	MONDO:0002009
autism spectrum disorder	3	MONDO:0005258	EFO:0003756
depressive disorder	3	MONDO:0002050	MONDO:0002050
bipolar disorder	3	MONDO:0004985	EFO:0009963
generalized anxiety disorder	2	MONDO:0001942	EFO:1001892

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

Clinical trials

Total trials: 46.

Phase distribution

Phase	Trials
PHASE3	20
PHASE2	11
PHASE4	6
PHASE2/PHASE3	5
PHASE1	3
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05913947	PHASE4	RECRUITING	Lithium Versus Cariprazine in the Acute Phase Treatment of Bipolar Depression (DUAG9)
NCT05933538	PHASE4	NOT_YET_RECRUITING	Effectiveness of Cariprazine Monotherapy for Treatment of Major Depressive Disorder
NCT06433635	PHASE4	ACTIVE_NOT_RECRUITING	Sequential Multiple Assignment Randomized Trial for Bipolar Depression
NCT04843423	PHASE4	UNKNOWN	Adjunct Treatment With Cariprazine for Adults With Attention-deficit/Hyperactivity Disorder
NCT05060549	PHASE4	WITHDRAWN	Dopamine D3 Receptor Occupancy in Bipolar Depression
NCT05384483	PHASE4	COMPLETED	Cariprazine Versus Placebo for Social Anxiety Disorder
NCT03817502	PHASE3	RECRUITING	Efficacy and Safety of Cariprazine in the Treatment of Adolescent Participants (13 to 17 Years of Age) With Schizophrenia
NCT04777357	PHASE3	RECRUITING	A Study to Assess Change in Disease Activity and Adverse Events (AEs) With Cariprazine in the Treatment of Depressive Episodes in Pediatric Participants Participants (10 to 17 Years of Age) With Bipolar I Disorder.
NCT01058096	PHASE3	COMPLETED	Safety and Efficacy of Cariprazine for Mania
NCT01058668	PHASE3	COMPLETED	Safety and Efficacy of Cariprazine for Bipolar I Disorder
NCT01059539	PHASE3	COMPLETED	Long-term Safety and Tolerability of Cariprazine for Bipolar I Disorder
NCT01104766	PHASE3	COMPLETED	Safety and Efficacy of Cariprazine in Patients With Schizophrenia
NCT01104779	PHASE3	COMPLETED	Safety and Efficacy of Cariprazine in Schizophrenia
NCT01104792	PHASE3	COMPLETED	Long-term Study of Cariprazine in Patients With Schizophrenia
NCT01412060	PHASE3	COMPLETED	A Study of Cariprazine in the Prevention of Relapse of Symptoms in Participants With Schizophrenia
NCT01625000	PHASE2/PHASE3	COMPLETED	Safety and Efficacy of MP-214 in Patients With Schizophrenia
NCT01625897	PHASE2/PHASE3	COMPLETED	A Long-Term Study of MP-214 in Patients With Chronic Phase or Elderly Schizophrenia
NCT01626859	PHASE2/PHASE3	COMPLETED	A Pharmacokinetic Study of MP-214 in Patients With Schizophrenia
NCT01626872	PHASE2/PHASE3	COMPLETED	Long-Term Study of MP-214 in Patients With Schizophrenia
NCT01626885	PHASE2/PHASE3	COMPLETED	A Long-Term Study of MP-214 in Patients With Receiving Multiple Drugs Schizophrenia
NCT01715805	PHASE3	COMPLETED	Efficacy, Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy (ADT) in Patients With Major Depressive Disorder (MDD)
NCT01838876	PHASE3	COMPLETED	Long-term Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy in Patients With Major Depressive Disorder
NCT02670538	PHASE3	COMPLETED	Study of the Efficacy of a Fixed-dose Regimen of Cariprazine Compared to Placebo for Treatment of the Depressive Episode in Participants With Bipolar I Disorder
NCT02670551	PHASE3	COMPLETED	Study on the Efficacy, Safety, and Tolerability of Cariprazine Relative to Placebo in Participants With Bipolar I Depression
NCT03573297	PHASE3	COMPLETED	A Cariprazine Study in the Prevention of Relapse in Bipolar I Disorder Patients Whose Current Episode is Manic or Depressive, With or Without Mixed Features
NCT03593213	PHASE3	TERMINATED	Clinical Trial Evaluating the Efficacy, Safety, and Tolerability of Cariprazine in a Dose-Reduction Paradigm in the Prevention of Relapse in Participants With Schizophrenia
NCT03738215	PHASE3	COMPLETED	Efficacy, Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy (ADT) in Patients With Major Depressive Disorder (MDD) Who Have Had an Inadequate Response to Antidepressants Alone
NCT03739203	PHASE3	COMPLETED	The Objective of This Study is to Evaluate the Efficacy, Safety and Tolerability of Cariprazine as an Adjunctive Treatment to Antidepressant Therapy (ADT) in Patients With Major Depressive Disorder (MDD) Who Have Had an Inadequate Response to Antidepressants Alone
NCT04771299	PHASE3	TERMINATED	Assessing the Role of Cariprazine in Improving Cognition in Euthymic Bipolar Patients
NCT05368558	PHASE3	TERMINATED	Study to Assess Adverse Events and Change in Disease Activity of Oral Cariprazine Capsules in Adult Participants With Schizophrenia
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT07185815	PHASE1/PHASE2	RECRUITING	Pharmacokinetics, Safety, Tolerability and Efficacy of a Subcutaneous Long-Acting Injection of Cariprazine (Cariprazine Depot) in Subjects Eligible for Treatment With Oral Cariprazine
NCT00404573	PHASE2	COMPLETED	Study Evaluating RGH-188 in the Treatment of Patients With Schizophrenia
NCT00488618	PHASE2	COMPLETED	Study Evaluating Cariprazine (RGH-188) in the Treatment of Patients With Acute Mania
NCT00694707	PHASE2	COMPLETED	Safety and Efficacy of Cariprazine (RGH-188) in the Acute Exacerbation of Schizophrenia
NCT00839852	PHASE2	COMPLETED	A Study of Cariprazine in Patients With Chronic Stable Schizophrenia
NCT00852202	PHASE2	COMPLETED	Safety and Efficacy of RGH-188 (Cariprazine) in Bipolar Depression
NCT00854100	PHASE2	COMPLETED	Safety and Efficacy of Cariprazine As Adjunctive Therapy In Major Depressive Disorder
NCT00862992	PHASE2	COMPLETED	Safety, Pharmacokinetics and Efficacy Study of MP-214 in Patients With Schizophrenia
NCT01396447	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of Cariprazine in Participants With Bipolar Depression

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 1 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.

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

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3
GENTIAN VIOLET	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
AMIODARONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
AMISULPRIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
AMLODIPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
AMOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
APOMORPHINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
ARMODAFINIL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
ASENAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
AZELASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BAZEDOXIFENE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BENPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BENZQUINAMIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BENZTROPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BEPRIDIL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BOSUTINIB	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BROMPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BUSPIRONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
BUTRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CABERGOLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CARVEDILOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CINACALCET	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CINNARIZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CISAPRIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CLEMASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CLOZAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DESIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DESLORATADINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DIBENZEPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DIETHYLSTILBESTROL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DIPHENIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DISULFIRAM	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DOBUTAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DOMPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DOPAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DOTHIEPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DOXEPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DROPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3
DULOXETINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
EBASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
ECONAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
EPALRESTAT	ChEMBL	Phase 4 (approved)	DRD2, DRD3
EPINEPHRINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
ERGOTAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3
FENOLDOPAM	ChEMBL	Phase 4 (approved)	DRD2, DRD3
FENTANYL	ChEMBL	Phase 4 (approved)	DRD2, DRD3