Asenapine

Summary

Asenapine (CHEMBL3187365) is an approved small molecule (ATC N05AH05) targeting HTR1A, DRD2, and HRH1; indicated across 3 conditions including psychotic disorder and bipolar disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AH05
• Targets: 7 (HTR1A, DRD2, HRH1…)
• Indications: 3 conditions
• Clinical trials: 42
• Chemistry: 285.8 Da · C17H16ClNO

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL3187365
Name	Asenapine
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	9903970
ChEBI	CHEBI:71255
ATC	N05AH05
Molecular formula	C17H16ClNO
Molecular weight	285.8
InChIKey	VSWBSWWIRNCQIJ-UHFFFAOYSA-N

SMILES: CN1CC2C(C1)C3=C(C=CC(=C3)Cl)OC4=CC=CC=C24

IUPAC name: 9-chloro-4-methyl-13-oxa-4-azatetracyclo[12.4.0.02,6.07,12]octadeca-1(18),7(12),8,10,14,16-hexaene

ChEBI definition: An organic heterotetracyclic compound that is 2,3,3a,12b-tetrahydrodibenzo[2,3:6,7]oxepino[4,5-c]pyrrole bearing methyl and chloro substituents at positions 2 and 5 respectively.

Also known as: Asenapina, Asenapine, Secuado, Sycrest, SID144207145, rel-Asenapine, SID170465569, SID124899263, ASENAPINE, asenapine

Parent form; salt/anhydrous children: CHEMBL3544974

Patent coverage: 74 distinct patent families (143 SureChEMBL compound mentions), from 4 matched compound structure(s). 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	Full agonist	8.3	0%	P08908
DRD2	D2 receptor	Antagonist	8.92	0%	P14416
HRH1	H1 receptor	Antagonist	9.8	0%	P35367
HTR1B	5-HT1B receptor	Full agonist	8.1	0.2%	P28222
HTR1D	5-HT1D receptor	Full agonist	8.4	0%	P28221
HTR1E	5-ht1e receptor	Full agonist	8	0%	P28566
HTR2A	5-HT2A receptor	Antagonist	10.22	0%	P28223

Broader ChEMBL bioactivity targets: 25 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, 5-hydroxytryptamine receptor 3A, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Sodium channel protein type 5 subunit alpha, D(1A) dopamine receptor, Adrenergic receptor alpha-1, Muscarinic acetylcholine receptor M2, 5-hydroxytryptamine receptor 1A.

Bioactivity

ChEMBL activities: 30 potent at pChembl ≥ 5 of 36 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2A	9.7	AC50	0.2	nM	CHEMBL_ACT_25225525
HTR2B	9.68	Ki	0.21	nM	CHEMBL_ACT_25630001
HTR6	9.6	Ki	0.25	nM	CHEMBL_ACT_15035159
HTR2C	9.22	AC50	0.6	nM	CHEMBL_ACT_25132182
HTR2A	9.04	Ki	0.91	nM	CHEMBL_ACT_12668587
HTR2A	9.04	Ki	0.91	nM	CHEMBL_ACT_12671438
HRH1	9	Ki	1	nM	CHEMBL_ACT_22435764
ADRA1D	8.92	Ki	1.2	nM	CHEMBL_ACT_22435770
HTR2B	8.89	AC50	1.3	nM	CHEMBL_ACT_25227892
ADRA2B	8.85	AC50	1.4	nM	CHEMBL_ACT_25144083
ADRA1A	8.85	AC50	1.4	nM	CHEMBL_ACT_25218354
HRH1	8.68	AC50	2.1	nM	CHEMBL_ACT_25212905
HTR2C	8.61	Ki	2.46	nM	CHEMBL_ACT_12668583
HTR2C	8.6	Ki	2.5	nM	CHEMBL_ACT_12671434
DRD3	8.36	AC50	4.4	nM	CHEMBL_ACT_25193913
DRD1	8.05	Ki	8.9	nM	CHEMBL_ACT_16447786
DRD2	8.05	Ki	8.9	nM	CHEMBL_ACT_16447789
DRD4	8.05	Ki	9	nM	CHEMBL_ACT_16447795
DRD3	8.03	Ki	9.4	nM	CHEMBL_ACT_16447792
HTR1A	8.01	AC50	9.7	nM	CHEMBL_ACT_25216282
DRD1	8	AC50	10	nM	CHEMBL_ACT_25115869
ADRA2A	7.86	AC50	13.7	nM	CHEMBL_ACT_25157090
DRD2	7.24	AC50	57	nM	CHEMBL_ACT_25140728
ADRA2A	7.1	AC50	79	nM	CHEMBL_ACT_25220263
DRD1	6.61	AC50	243.5	nM	CHEMBL_ACT_25181287
ADRA2C	6.52	AC50	300	nM	CHEMBL_ACT_25148273
Q01827	5.98	AC50	1051	nM	CHEMBL_ACT_25197395
SCN5A	5.7	AC50	2000	nM	CHEMBL_ACT_25158986
KCNH2	5.58	AC50	2600	nM	CHEMBL_ACT_25118421
GABRA1	5.19	AC50	6500	nM	CHEMBL_ACT_25234464

Target pathways

Aggregated over 7 target gene(s): HTR1A, DRD2, HRH1, HTR1B, HTR1D, HTR1E, HTR2A.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	5	HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
Signaling by GPCR	5	HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
Class A/1 (Rhodopsin-like receptors)	5	HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
Amine ligand-binding receptors	5	HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
Serotonin receptors	5	HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
GPCR ligand binding	5	HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
GPCR downstream signalling	4	HTR1B, HTR1D, HTR1E, HTR2A
G alpha (i) signalling events	3	HTR1B, HTR1D, HTR1E
G alpha (q) signalling events	2	HRH1, HTR2A
Histamine receptors	1	HRH1
Dopamine receptors	1	DRD2

Dominant GO biological processes

GO term	Targets
G protein-coupled receptor signaling pathway	7
signal transduction	7
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	6
chemical synaptic transmission	6
adenylate cyclase-inhibiting serotonin receptor signaling pathway	4
regulation of behavior	3
adenylate cyclase-activating G protein-coupled receptor signaling pathway	3
phospholipase C-activating serotonin receptor signaling pathway	3
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	3
serotonin receptor signaling pathway	2
positive regulation of cell population proliferation	2
adult behavior	2
G protein-coupled serotonin receptor signaling pathway	2
temperature homeostasis	2
intracellular calcium ion homeostasis	2

Indications & clinical

Indications

3 indications (3 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	4	MONDO:0004985	EFO:0009963

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

Clinical trials

Total trials: 42.

Phase distribution

Phase	Trials
PHASE3	31
PHASE4	5
Not specified	3
PHASE1	2
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07047651	PHASE4	ACTIVE_NOT_RECRUITING	Τhe Combination of Pharmacotherapy With RECOVERYTRSGR and RECOVERYTRSBDGR.
NCT01400113	PHASE4	COMPLETED	Treating Acutely Agitated Patients With Asenapine Sublingual Tablets
NCT01460290	PHASE4	COMPLETED	Asenapine in the Treatment of Older Adults With Bipolar Disorder
NCT01587118	PHASE4	COMPLETED	An Open Label Pilot Study of Adjunctive Asenapine for the Treatment of Posttraumatic Stress Disorder
NCT01968161	PHASE4	UNKNOWN	Investigator Initiated Study - Asenapine Early Psychosis
NCT00143182	PHASE3	COMPLETED	9 Week Extension Study of Asenapine and Olanzapine in Treatment of Mania (P07007)(COMPLETED)
NCT00145470	PHASE3	COMPLETED	12 Week Study of the Safety/Efficacy of Asenapine When Added to Lithium/Valproate in the Treatment of Bipolar Disorder (A7501008 / P05844 / MK-8274-017)
NCT00145496	PHASE3	COMPLETED	Efficacy and Safety of Asenapine Compared With Olanzapine in Patients With Persistent Negative Symptoms of Schizophrenia (A7501013)(COMPLETED)(P05771)
NCT00145509	PHASE3	COMPLETED	40 Week Trial to Study the Safety of Asenapine When Added to Lithium or Valproate in the Treatment of Bipolar Disorder (A7501009)(P05786)
NCT00151424	PHASE3	COMPLETED	Efficacy and Safety of Asenapine With Placebo and Olanzapine (41022)(P05947)
NCT00156065	PHASE3	COMPLETED	Long-Term Efficacy and Safety of Asenapine Using Haloperidol as a Positive Control (41513)(COMPLETED)(P05785)
NCT00156091	PHASE3	COMPLETED	Long-Term Efficacy and Safety of Asenapine Using Olanzapine as a Positive Control (41512)(COMPLETED)(P05784)
NCT00156104	PHASE3	COMPLETED	Efficacy and Safety of Asenapine With Placebo and Haloperidol (41023)(P05926)(COMPLETED)
NCT00156117	PHASE3	COMPLETED	Efficacy and Safety of Asenapine With Placebo and Olanzapine (41021)(P05933)
NCT00159744	PHASE3	COMPLETED	3-Week Study of Asenapine, Olanzapine and Placebo for Treatment of Bipolar Mania (P07008)
NCT00159783	PHASE3	COMPLETED	40 Week Extension Study Of Asenapine and Olanzapine For Bipolar Disorder (A7501007)(COMPLETED)(P05857)
NCT00159796	PHASE3	COMPLETED	3-week Study of Asenapine, Olanzapine and Placebo for Treatment of Bipolar Mania (P07009)
NCT00174265	PHASE3	COMPLETED	6-Month Extension Trial of Asenapine With Olanzapine in Negative Symptoms Patients Who Completed the First 6- Month Trial (A7501014)(COMPLETED)(P05772)
NCT00212771	PHASE3	COMPLETED	Efficacy and Safety of Asenapine Using an Active Control in Subjects With Schizophrenia or Schizoaffective Disorder (25520)(P05846)
NCT00212784	PHASE3	COMPLETED	Efficacy and Safety of Asenapine Using an Active Control in Subjects With Schizophrenia or Schizoaffective Disorder (25517)(P05935)
NCT00212836	PHASE3	COMPLETED	Efficacy and Safety of Asenapine Compared With Olanzapine in Patients With Persistent Negative Symptoms of Schizophrenia (25543)(COMPLETED)(P05817)
NCT00265343	PHASE3	COMPLETED	6-Month Extension Trial of Asenapine With Olanzapine in Negative Symptom Patients Who Completed the Protocol 25543 (25544)(P05777)
NCT00281320	PHASE3	COMPLETED	Study of Asenapine in Elderly Subjects With Psychosis (A7501021)(P05717)
NCT00764478	PHASE3	COMPLETED	Fixed-dose Safety and Efficacy Study of Asenapine for the Treatment of Acute Manic or Mixed Episode in Bipolar 1 Disorder (P05691)
NCT01098110	PHASE3	COMPLETED	6-week Trial of the Efficacy and Safety of Asenapine Compared to Placebo in Participants With an Acute Exacerbation of Schizophrenia (P06124)
NCT01142596	PHASE3	COMPLETED	Long-term Extension Trial of Asenapine in Subjects With Schizophrenia (Study P06125)
NCT01190254	PHASE3	COMPLETED	Fixed Dose Efficacy and Safety Study of Asenapine for the Treatment of Schizophrenia in Adolescents (P05896)
NCT01190267	PHASE3	COMPLETED	Flexible Dose, Long-term Safety Study of Asenapine for the Treatment of Schizophrenia in Adolescents (P05897)
NCT01244815	PHASE3	COMPLETED	Efficacy and Safety of Asenapine Treatment for Pediatric Bipolar Disorder (P06107 Has an Extension [P05898; NCT01349907])(P06107)
NCT01244828	PHASE3	COMPLETED	Long-term Study of Asenapine in Participants With Residual Subtype, Receiving Multiple or/and High Dose Drugs, or Treatment Refractory Schizophrenia (P06238)
NCT01349907	PHASE3	COMPLETED	Extension Study of Asenapine [P06107 (NCT01244815)] for Pediatric Bipolar Disorder (P05898)
NCT01395992	PHASE3	COMPLETED	Long-Term Safety Extension Trial of Asenapine in Bipolar 1 Disorder Participants Who Completed Protocol P05691 (P05692)
NCT01396291	PHASE3	COMPLETED	Efficacy and Safety of Asenapine in the Prevention of Recurrence of Mood Episodes in Participants With Bipolar 1 Disorder (P06384)
NCT01617187	PHASE3	COMPLETED	A Study of the Efficacy and Safety of Asenapine in Participants With an Acute Exacerbation of Schizophrenia (P05688)
NCT01617200	PHASE3	COMPLETED	Long-Term Safety Extension Trial of Asenapine in Schizophrenia Participants Who Completed Protocol P05688 (P05689)
NCT01684657	PHASE3	SUSPENDED	A Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Tolerability of Asenapine With Flexible Dosing From 5mg to 20mg in Adults With Developmental Stuttering
NCT01807741	PHASE2	TERMINATED	Asenapine for Bipolar Depression
NCT01206517	PHASE1	COMPLETED	A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of Sublingual Asenapine in a Pediatric Population With Schizophrenia or Bipolar I Disorder (P06522 AM1)
NCT01948024	PHASE1	COMPLETED	Bio-equivalence Study Between SAPHRIS and Asenapine
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 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.

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

Molecule	Source	Status	Shared targets
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
IMIPRAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
RISPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1E, HTR2A
ERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1E, HTR2A
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1E, HTR2A
RIZATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HRH1, HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1D, HTR2A
AZELASTINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1B, HTR1D, HTR1E, HTR2A
CARIPRAZINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1D, HTR2A
KETANSERIN	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1D, HTR2A
NEFAZODONE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1D, HTR2A
YOHIMBINE	ChEMBL + PubChem	Phase 3 (approved)	DRD2, HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
LYSERGIDE	ChEMBL	Phase 2	DRD2, HRH1, HTR1A, HTR1D, HTR1E, HTR2A
RITANSERIN	ChEMBL	Phase 2	DRD2, HRH1, HTR1A, HTR1B, HTR1E, HTR2A
CYPROHEPTADINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1E, HTR2A
METHYLERGONOVINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1E, HTR2A
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1B, HTR1D, HTR2A
QUETIAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1E, HTR2A
SUMATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
ZIPRASIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1E, HTR2A
ZOLMITRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
CINACALCET	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1D, HTR2A
FROVATRIPTAN	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR1B, HTR1D, HTR1E
MIANSERIN	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1D, HTR2A
SALMETEROL	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR1B, HTR1D, HTR2A
SERTINDOLE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR2A
SILODOSIN	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1D
VILAZODONE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR1B, HTR1D
XYLOMETAZOLINE	ChEMBL	Phase 4 (approved)	DRD2, HTR1A, HTR1B, HTR1D, HTR2A
SEROTONIN	ChEMBL + PubChem	Phase 3 (approved)	HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
LATREPIRDINE	ChEMBL	Phase 3	DRD2, HRH1, HTR1D, HTR1E, HTR2A
GSK163090	ChEMBL	Phase 2	DRD2, HTR1A, HTR1B, HTR1D, HTR2A
MEBUFOTENIN	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
PENFLURIDOL	ChEMBL	Phase 2	DRD2, HRH1, HTR1A, HTR1D, HTR2A
PSILOCIN	ChEMBL	Phase 2	HTR1A, HTR1B, HTR1D, HTR1E, HTR2A
SPIRAMIDE	ChEMBL	Phase 2	DRD2, HRH1, HTR1A, HTR1D, HTR2A
CANNABIDIOL	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HTR1A, HTR1E, HTR2A
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
Fidaxomicin	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
NARATRIPTAN	ChEMBL + PubChem	Phase 4 (approved)	HTR1A, HTR1B, HTR1D, HTR1E
Propoxyphene	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
TAMSULOSIN	ChEMBL + PubChem	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
AMOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
APOMORPHINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
AZATADINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
BENPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
BROMPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
BUSPIRONE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
CABERGOLINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
CINNARIZINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
CISAPRIDE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
CLEMASTINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR1A, HTR2A