Zuclopenthixol

Summary

Zuclopenthixol (CHEMBL53904) is a phase-3 clinical-stage small-molecule dopaminergic antagonist (ATC N05AF05); indicated across 5 conditions including psychotic disorder and anxiety.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• ATC class: N05AF05
• Indications: 5 conditions
• Clinical trials: 5
• Chemistry: 401 Da · C22H25ClN2OS

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL53904
Name	Zuclopenthixol
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	5311507
ChEBI	CHEBI:51364
ATC	N05AF05
Molecular formula	C22H25ClN2OS
Molecular weight	401
InChIKey	WFPIAZLQTJBIFN-DVZOWYKESA-N

SMILES: C1CN(CCN1CC/C=C\2/C3=CC=CC=C3SC4=C2C=C(C=C4)Cl)CCO

IUPAC name: 2-[4-[(3Z)-3-(2-chlorothioxanthen-9-ylidene)propyl]piperazin-1-yl]ethanol

ChEBI definition: The (Z)-isomer of clopenthixol.

Pharmacological roles (ChEBI): dopaminergic antagonist, α-adrenergic antagonist, serotonergic antagonist, H1-receptor antagonist, first generation antipsychotic.

Also known as: Clopenthixol cis(z)-form, Clopixol, Zoclopenthixol, Zuclopenthixol, Zuclopentixol, SID11112430, ZUCLOPENTHIXOL, zuclopenthixol, ZUCLOPENTHIXOL_CLOPENTHIXOL

Parent form; salt/anhydrous children: CHEMBL1437855, CHEMBL2360084

Patent coverage: 1,091 distinct patent families (4,088 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 3,991 (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

Broader ChEMBL bioactivity targets: 25 (assay-derived). Sample: Ubiquitin carboxyl-terminal hydrolase 2, Nuclear receptor ROR-gamma, Prelamin-A/C, 5-hydroxytryptamine receptor 2B, Protein deacetylase HDAC6, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, 5-hydroxytryptamine receptor 1A, D(2) dopamine receptor.

Bioactivity

ChEMBL activities: 26 potent at pChembl ≥ 5 of 32 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HTR2A	8.34	AC50	4.6	nM	CHEMBL_ACT_25173512
ADRA1A	7.94	AC50	11.4	nM	CHEMBL_ACT_25137755
HTR2B	7.84	AC50	14.4	nM	CHEMBL_ACT_25164030
HRH1	7.55	AC50	28	nM	CHEMBL_ACT_25212204
DRD2	7.35	AC50	45	nM	CHEMBL_ACT_25140028
DRD3	7.34	AC50	46	nM	CHEMBL_ACT_25193230
ADRA2C	6.8	AC50	160	nM	CHEMBL_ACT_25147571
HTR6	6.77	Ki	169	nM	CHEMBL_ACT_12059587
ADRA2B	6.5	AC50	320	nM	CHEMBL_ACT_25143405
HTR2A	6.29	AC50	510	nM	CHEMBL_ACT_25224896
KCNH2	6.05	AC50	900	nM	CHEMBL_ACT_25117414
HTR2B	6.04	AC50	920	nM	CHEMBL_ACT_25227244
SLC6A3	6	AC50	1000	nM	CHEMBL_ACT_25123650
HTR2C	6	AC50	1000	nM	CHEMBL_ACT_25131512
LMNA	5.95	Potency	1122	nM	CHEMBL_ACT_3641502
OPRK1	5.71	AC50	1942	nM	CHEMBL_ACT_25129155
P51450	5.65	Potency	2239	nM	CHEMBL_ACT_4089136
CYP2C19	5.6	Potency	2512	nM	CHEMBL_ACT_4020285
CYP2C19	5.6	AC50	2512	nM	CHEMBL_ACT_6012874
HDAC6	5.47	IC50	3377	nM	CHEMBL_ACT_23141103
HTR1A	5.19	AC50	6400	nM	CHEMBL_ACT_25215806
ADRA2A	5.14	AC50	7300	nM	CHEMBL_ACT_25219610
ADRA2A	5.13	AC50	7343	nM	CHEMBL_ACT_25155862
SLC6A4	5.08	AC50	8400	nM	CHEMBL_ACT_25150042
CYP2D6	5	Potency	10000	nM	CHEMBL_ACT_4994302
CYP2D6	5	AC50	10000	nM	CHEMBL_ACT_6041772

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

5 indications (0 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	3	MONDO:0005485	EFO:0005407
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: 5.

Phase distribution

Phase	Trials
PHASE4	3
PHASE3	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07047651	PHASE4	ACTIVE_NOT_RECRUITING	Τhe Combination of Pharmacotherapy With RECOVERYTRSGR and RECOVERYTRSBDGR.
NCT00767715	PHASE4	TERMINATED	A Study in the Treatment of Acute Mania
NCT02307396	PHASE4	COMPLETED	Evaluation of the Necessity of Long-term Pharmacological Treatment With Antipsychotics in Schizophrenic Patients
NCT02374567	PHASE3	TERMINATED	Pharmacovigilance in Gerontopsychiatric Patients
NCT00206960	Not specified	COMPLETED	Dopaminergic, Functional, Structural, and Cognitive Disturbances in First-episode Schizophrenia

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (1) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of DPWG Guideline for zuclopenthixol and CYP2D6	DPWG	CYP2D6	yes	yes

PharmGKB also curates 1 clinical and 11 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).