Chlorprothixene

Summary

Chlorprothixene (CHEMBL908) is an approved small molecule (ATC N05AF03) targeting DRD2, DRD3, and HRH1; indicated across 5 conditions including psychotic disorder and anxiety.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AF03
• Targets: 3 (DRD2, DRD3, HRH1)
• Indications: 5 conditions
• Clinical trials: 2
• Chemistry: 315.9 Da · C18H18ClNS

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL908
Name	Chlorprothixene
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	667467
ChEBI	CHEBI:50931
ATC	N05AF03
Molecular formula	C18H18ClNS
Molecular weight	315.9
InChIKey	WSPOMRSOLSGNFJ-AUWJEWJLSA-N

SMILES: CN(C)CC/C=C\1/C2=CC=CC=C2SC3=C1C=C(C=C3)Cl

IUPAC name: (3Z)-3-(2-chlorothioxanthen-9-ylidene)-N,N-dimethylpropan-1-amine

ChEBI definition: A chlorprothixene in which the double bond adopts a (Z)-configuration.

Also known as: Chlorprothixene, Clorprotixeno, N-714, NSC-18720, RO-40403, Taractan, Truxal, chlorprothixene, Chlorprotixen, SID29217891, CHLORPROTHIXENE, SID26665646

Parent form; salt/anhydrous children: CHEMBL1256658

Patent coverage: 2,639 distinct patent families (9,322 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 9,275 (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
DRD2	D2 receptor	Antagonist	8.53	0%	P14416
DRD3	D3 receptor	Antagonist	8.34	0%	P35462
HRH1	H1 receptor	Antagonist	8.43	0%	P35367

Broader ChEMBL bioactivity targets: 32 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Pleiotropic ABC efflux transporter of multiple drugs, D(1B) dopamine receptor, Alpha-2A adrenergic receptor, D(1A) dopamine receptor, Thromboxane A2 receptor, Muscarinic acetylcholine receptor M2, Beta-1 adrenergic receptor, 5-hydroxytryptamine receptor 1A, Muscarinic acetylcholine receptor M1, D(2) dopamine receptor, Motilin receptor, Prostaglandin G/H synthase 1, Sodium-dependent noradrenaline transporter, Sodium-dependent serotonin transporter, Alpha-1A adrenergic receptor, Histamine H1 receptor, Mu-type opioid receptor, D(3) dopamine receptor, Sodium-dependent dopamine transporter.

Bioactivity

ChEMBL activities: 28 potent at pChembl ≥ 5 of 41 total. Top 100 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HRH1	9	IC50	1	nM	CHEMBL_ACT_12085946
P31390	8.97	IC50	1.07	nM	CHEMBL_ACT_12085963
DRD2	8.53	Ki	2.96	nM	CHEMBL_ACT_2601042
DRD1	8.52	AC50	3	nM	CHEMBL_ACT_25114912
DRD3	8.52	AC50	3	nM	CHEMBL_ACT_25194234
HTR6	8.52	Ki	3	nM	CHEMBL_ACT_78161
ADRA1A	8.46	AC50	3.5	nM	CHEMBL_ACT_25218594
HRH1	8.43	Ki	3.75	nM	CHEMBL_ACT_2601000
DRD3	8.34	Ki	4.56	nM	CHEMBL_ACT_2601056
P32305	8.25	Ki	5.6	nM	CHEMBL_ACT_78162
DRD5	8.05	Ki	9	nM	CHEMBL_ACT_2601028
SLC6A2	8	AC50	10	nM	CHEMBL_ACT_25145702
DRD1	7.75	Ki	18	nM	CHEMBL_ACT_2602062
CHRM2	7.22	AC50	60	nM	CHEMBL_ACT_25195438
HTR1A	6.96	AC50	110	nM	CHEMBL_ACT_25164726
CHRM1	6.92	AC50	120	nM	CHEMBL_ACT_25209952
SLC6A4	6.77	AC50	170	nM	CHEMBL_ACT_25149829
SLC6A2	6.63	AC50	234.9	nM	CHEMBL_ACT_25144493
SLC6A4	6.58	AC50	260	nM	CHEMBL_ACT_25151029
KCNH2	6.42	AC50	380	nM	CHEMBL_ACT_25117082
ADRA2A	6.28	AC50	520	nM	CHEMBL_ACT_25156131
HRH1	6.06	IC50	871	nM	CHEMBL_ACT_12085954
OPRM1	5.46	AC50	3470	nM	CHEMBL_ACT_25157877
SLC6A3	5.3	AC50	4980	nM	CHEMBL_ACT_25124661
P33302	5.29	IC50	5100	nM	CHEMBL_ACT_5306654
PTGS1	5.26	AC50	5500	nM	CHEMBL_ACT_25204926
TBXA2R	5.06	AC50	8710	nM	CHEMBL_ACT_25197565
PTGS1	5.06	AC50	8690	nM	CHEMBL_ACT_25205859

Target pathways

Aggregated over 3 target gene(s): DRD2, DRD3, HRH1.

Top Reactome pathways

4 total, by targets touching each:

Pathway	Targets	Genes
Dopamine receptors	2	DRD2, DRD3
Histamine receptors	1	HRH1
G alpha (q) signalling events	1	HRH1
G alpha (i) signalling events	1	DRD3

Dominant GO biological processes

GO term	Targets
visual learning	3
signal transduction	3
G protein-coupled receptor signaling pathway	3
G protein-coupled receptor internalization	2
intracellular calcium ion homeostasis	2
adenylate cyclase-inhibiting dopamine receptor signaling pathway	2
phospholipase C-activating G protein-coupled receptor signaling pathway	2
locomotory behavior	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

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
anxiety	3	MONDO:0011918	EFO:0005230
dementia	3	MONDO:0001627	HP:0000726
depressive disorder	3	MONDO:0002050	MONDO:0002050

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

Clinical trials

Total trials: 2.

Phase distribution

Phase	Trials
PHASE3	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02374567	PHASE3	TERMINATED	Pharmacovigilance in Gerontopsychiatric Patients
NCT03449485	Not specified	RECRUITING	Bariatric Surgery and Pharmacokinetics of Chlorprothixene

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.

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

Molecule	Source	Status	Shared targets
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, HRH1
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, HRH1
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, HRH1
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, HRH1
TAMSULOSIN	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD3, HRH1
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
AMIODARONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
AMISULPRIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
AMOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
APOMORPHINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
ASENAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
AZELASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
BENPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
BENZTROPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
BEPRIDIL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
BROMPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
BUSPIRONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
BUTRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
CABERGOLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
CARIPRAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
CINACALCET	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
CINNARIZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
CISAPRIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
CLEMASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
CLOZAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
CYCLOBENZAPRINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
DAUNORUBICIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
DESIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
DIBENZEPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
DOMPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
DOTHIEPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
DOXEPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
DROPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
DULOXETINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
EBASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
EPALRESTAT	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
FENTANYL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
FEXOFENADINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
HALOPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
HYDROXYZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
IDARUBICIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
ILOPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
IMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
INDOCYANINE GREEN ACID FORM	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
IPRINDOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
KETANSERIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
KETOTIFEN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
LASOFOXIFENE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
LOFEPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
LOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
LURASIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
MAPROTILINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
MASOPROCOL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
MECLIZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
METHYLERGONOVINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
METHYSERGIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
MIANSERIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
NAFTOPIDIL	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
NEFAZODONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
NITROXOLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
OLANZAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
OXAPROZIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PERGOLIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PERPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PHENAZOPYRIDINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PHENOXYBENZAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PIMOZIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PIPAMAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PIPERACETAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PONATINIB	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PRENYLAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PROCHLORPERAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PROMETHAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PROPIOMAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
PROTRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
QUETIAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
QUINAGOLIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
RIFAMPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
RISPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
ROPINIROLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
ROTIGOTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
SERTINDOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
SERTRALINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
SILODOSIN	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
SIROLIMUS	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
SUNITINIB	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
TERFENADINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1
THIETHYLPERAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD3, HRH1