Trifluoperazine

Summary

Trifluoperazine (CHEMBL422) is an approved small-molecule phenothiazine antipsychotic drug (ATC N05AB06) targeting DRD2, DRD4, and HRH1; indicated across 2 conditions including psychotic disorder and diamond-blackfan anemia.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AB06
• Targets: 5 (DRD2, DRD4, HRH1…)
• Indications: 2 conditions
• Clinical trials: 2
• Chemistry: 407.5 Da · C21H24F3N3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL422
Name	Trifluoperazine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5566
ChEBI	CHEBI:45951
ATC	N05AB06
Molecular formula	C21H24F3N3S
Molecular weight	407.5
InChIKey	ZEWQUBUPAILYHI-UHFFFAOYSA-N

SMILES: CN1CCN(CC1)CCCN2C3=CC=CC=C3SC4=C2C=C(C=C4)C(F)(F)F

IUPAC name: 10-[3-(4-methylpiperazin-1-yl)propyl]-2-(trifluoromethyl)phenothiazine

ChEBI definition: A member of the class of phenothiazines that is phenothiazine having a trifluoromethyl subsitituent at the 2-position and a 3-(4-methylpiperazin-1-yl)propyl group at the N-10 position.

Pharmacological roles (ChEBI): phenothiazine antipsychotic drug, dopaminergic antagonist, antiemetic, EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor, EC 5.3.3.5 (cholestenol Δ-isomerase) inhibitor, calmodulin antagonist.

Also known as: Amylozine, Apo-trifluoperazine, Flurazine, NSC-17474, NSC-46061, RP-7623, Stelazine, Stelazine fte, Trifluoperazina, Trifluoperazine, trifluoperazine, trifluoroperazine

Parent form; salt/anhydrous children: CHEMBL1710, CHEMBL1257040, CHEMBL1726794

Patent coverage: 5,711 distinct patent families (20,044 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 20,024 (100%) 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	9.02	0%	P14416
DRD4	D4 receptor	Antagonist	7.36	0%	P21917
HRH1	H1 receptor	Antagonist	7.2	0%	P35367
HTR2A	5-HT2A receptor	Antagonist	7.9	0%	P28223
HTR2C	5-HT2C receptor	Antagonist	6.4	0%	P28335

Broader ChEMBL bioactivity targets: 75 (assay-derived). Sample: Microtubule-associated protein tau, Survival motor neuron protein, Prelamin-A/C, Inositol monophosphatase 1, 4’-phosphopantetheinyl transferase ffp, Thrombopoietin, NPC intracellular cholesterol transporter 1, Ras-related protein Rab-9A, Pleiotropic ABC efflux transporter of multiple drugs, Vasopressin V2 receptor.

Bioactivity

ChEMBL activities: 74 potent at pChembl ≥ 5 of 120 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P61169	9.27	Kd	0.53	nM	CHEMBL_ACT_572761
P08909	8.98	Kd	1.04	nM	CHEMBL_ACT_572763
P61169	8.66	Ki	2.2	nM	CHEMBL_ACT_312098
EBPL	8.41	Ki	3.9	nM	CHEMBL_ACT_12633688
P08909	8.28	Ki	5.2	nM	CHEMBL_ACT_312101
EBP	8.1	Ki	8	nM	CHEMBL_ACT_1483859
DRD2	7.83	AC50	14.8	nM	CHEMBL_ACT_25140800
SIGMAR1	7.82	Ki	15	nM	CHEMBL_ACT_1483860
P61169	7.8	IC50	16	nM	CHEMBL_ACT_572755
HTR2A	7.78	AC50	16.5	nM	CHEMBL_ACT_25173763
DRD3	7.69	AC50	20.3	nM	CHEMBL_ACT_25193983
P15823	7.53	Ki	29.3	nM	CHEMBL_ACT_312102
ADRA1A	7.26	AC50	54.8	nM	CHEMBL_ACT_25138183
HTR2B	7.07	AC50	84.4	nM	CHEMBL_ACT_25164231
HRH1	6.95	AC50	112	nM	CHEMBL_ACT_25212978
DRD1	6.89	AC50	129.3	nM	CHEMBL_ACT_25114847
HSD17B10	6.7	Potency	199.5	nM	CHEMBL_ACT_4857430
CYP2D6	6.5	Potency	316.2	nM	CHEMBL_ACT_4994255
P15823	6.46	IC50	350	nM	CHEMBL_ACT_572756
P19327	6.39	Ki	411	nM	CHEMBL_ACT_312100
DRD1	6.35	AC50	450	nM	CHEMBL_ACT_25181296
HRH2	6.33	AC50	470.2	nM	CHEMBL_ACT_25114546
P32352	6.3	Ki	500	nM	CHEMBL_ACT_1483861
CYP1A2	6.2	AC50	631	nM	CHEMBL_ACT_6029529
KCNH2	6.13	AC50	749	nM	CHEMBL_ACT_25118524
HTR2A	6.11	AC50	774.6	nM	CHEMBL_ACT_25225592
ADRA2B	6.01	AC50	979.8	nM	CHEMBL_ACT_25144154
CALM1	6	Kd	1000	nM	CHEMBL_ACT_2358719
CYP2D6	6	Potency	1000	nM	CHEMBL_ACT_4957660
CYP1A2	6	AC50	1000	nM	CHEMBL_ACT_6042638

Target pathways

Aggregated over 5 target gene(s): DRD2, DRD4, HRH1, HTR2A, HTR2C.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
G alpha (q) signalling events	3	HRH1, HTR2A, HTR2C
Signal Transduction	2	HTR2A, HTR2C
Signaling by GPCR	2	HTR2A, HTR2C
Class A/1 (Rhodopsin-like receptors)	2	HTR2A, HTR2C
Amine ligand-binding receptors	2	HTR2A, HTR2C
GPCR downstream signalling	2	HTR2A, HTR2C
Dopamine receptors	2	DRD2, DRD4
Serotonin receptors	2	HTR2A, HTR2C
GPCR ligand binding	2	HTR2A, HTR2C
Histamine receptors	1	HRH1
G alpha (i) signalling events	1	DRD4

Dominant GO biological processes

GO term	Targets
signal transduction	5
G protein-coupled receptor signaling pathway	5
intracellular calcium ion homeostasis	4
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	4
chemical synaptic transmission	4
phospholipase C-activating G protein-coupled receptor signaling pathway	3
behavioral response to cocaine	3
release of sequestered calcium ion into cytosol	3
positive regulation of ERK1 and ERK2 cascade	3
G protein-coupled serotonin receptor signaling pathway	3
phospholipase C-activating serotonin receptor signaling pathway	3
temperature homeostasis	2
response to amphetamine	2
adenylate cyclase-inhibiting dopamine receptor signaling pathway	2
locomotory behavior	2

Indications & clinical

Indications

2 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
Diamond-Blackfan anemia	1	MONDO:0015253	MONDO:0015253

Clinical trials

Total trials: 2.

Phase distribution

Phase	Trials
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03966053	PHASE1/PHASE2	TERMINATED	The Use of Trifluoperazine in Transfusion Dependent DBA
NCT02600741	Not specified	COMPLETED	Family Intervention in Recent Onset Schizophrenia Treatment (FIRST)

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 2 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.

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

Molecule	Source	Status	Shared targets
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
Fidaxomicin	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
Propoxyphene	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
AMIODARONE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
AMOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
APOMORPHINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
ASENAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
BENPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
CARIPRAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
CLOZAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
DOXEPIN	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
EBASTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
FLUPHENAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
HALOPERIDOL	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
ILOPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
IMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
IPRINDOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
KETANSERIN	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
LOXAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
MIANSERIN	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
NEFAZODONE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
OLANZAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
PERGOLIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
PIMOZIDE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
PROCHLORPERAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
PROMAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
PROMETHAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
QUETIAPINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
RISPERIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
SERTINDOLE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
SUNITINIB	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
THIORIDAZINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
THIOTHIXENE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
TRAZODONE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A, HTR2C
LISURIDE	ChEMBL	Phase 3	DRD2, DRD4, HRH1, HTR2A, HTR2C
FANANSERIN	ChEMBL	Phase 2	DRD2, DRD4, HRH1, HTR2A, HTR2C
LYSERGIDE	ChEMBL	Phase 2	DRD2, DRD4, HRH1, HTR2A, HTR2C
NEMONAPRIDE	ChEMBL	Phase 2	DRD2, DRD4, HRH1, HTR2A, HTR2C
PENFLURIDOL	ChEMBL	Phase 2	DRD2, DRD4, HRH1, HTR2A, HTR2C
RITANSERIN	ChEMBL	Phase 2	DRD2, DRD4, HRH1, HTR2A, HTR2C
SPIPERONE	ChEMBL	Phase 2	DRD2, DRD4, HRH1, HTR2A, HTR2C
ZOTEPINE	ChEMBL	Phase 2	DRD2, DRD4, HRH1, HTR2A, HTR2C
Pyrazinamide	PubChem	Approved	DRD2, DRD4, HRH1, HTR2A, HTR2C
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A
AZATADINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR2A, HTR2C
AZELASTINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR2A, HTR2C
BENZTROPINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR2A, HTR2C
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HTR2A, HTR2C
BUSPIRONE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR2A, HTR2C
BUTRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR2A, HTR2C
CABERGOLINE	ChEMBL	Phase 4 (approved)	DRD2, DRD4, HRH1, HTR2A