Fluphenazine

Summary

Fluphenazine (CHEMBL726) is an approved small-molecule phenothiazine antipsychotic drug (ATC N05AB02) targeting HTR6, HTR7, and DRD1; indicated across 2 conditions including psychotic disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N05AB02
• Targets: 7 (HTR6, HTR7, DRD1…)
• Indications: 2 conditions
• Clinical trials: 7
• Chemistry: 437.5 Da · C22H26F3N3OS

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL726
Name	Fluphenazine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3372
ChEBI	CHEBI:5123
ATC	N05AB02
Molecular formula	C22H26F3N3OS
Molecular weight	437.5
InChIKey	PLDUPXSUYLZYBN-UHFFFAOYSA-N

SMILES: C1CN(CCN1CCCN2C3=CC=CC=C3SC4=C2C=C(C=C4)C(F)(F)F)CCO

IUPAC name: 2-[4-[3-[2-(trifluoromethyl)phenothiazin-10-yl]propyl]piperazin-1-yl]ethanol

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

Pharmacological roles (ChEBI): phenothiazine antipsychotic drug, dopaminergic antagonist, anticoronaviral agent.

Also known as: Flufenazina, Fluphenazine, NSC-62323, Flufenazine, fluphenazine, SID11111179, SID11111180, SID26751625, SID57287813, SID90341540, SID104171155, SID50100242

Parent form; salt/anhydrous children: CHEMBL1200792, CHEMBL1448187

Patent coverage: 6,335 distinct patent families (23,313 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 23,026 (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
HTR6	5-HT6 receptor	Inverse agonist	7.4	0.2%	P50406
HTR7	5-HT7 receptor	Inverse agonist	7.9	0.8%	P34969
DRD1	D1 receptor	Antagonist	7.7	0%	P21728
DRD2	D2 receptor	Antagonist	8.84	0%	P14416
DRD5	D5 receptor	Antagonist	7.9	0%	P21918
HRH1	H1 receptor	Antagonist	7.7	0%	P35367
HTR2A	5-HT2A receptor	Antagonist	7.5	0%	P28223

Broader ChEMBL bioactivity targets: 69 (assay-derived). Sample: Microtubule-associated protein tau, Ubiquitin carboxyl-terminal hydrolase 2, Prelamin-A/C, Inositol monophosphatase 1, 4’-phosphopantetheinyl transferase ffp, Thrombopoietin, Pleiotropic ABC efflux transporter of multiple drugs, Muscarinic acetylcholine receptor M4, Receptor tyrosine-protein kinase erbB-2, 5-hydroxytryptamine receptor 2B.

Bioactivity

ChEMBL activities: 119 potent at pChembl ≥ 5 of 166 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
DRD3	9.7	Ki	0.2	nM	CHEMBL_ACT_7667941
DRD2	9.27	Ki	0.54	nM	CHEMBL_ACT_7667939
DRD3	9.23	IC50	0.59	nM	CHEMBL_ACT_7667940
DRD2	8.84	Ki	1.44	nM	CHEMBL_ACT_25917641
DRD2	8.84	Ki	1.44	nM	CHEMBL_ACT_2601046
HTR2A	8.84	Ki	1.46	nM	CHEMBL_ACT_7670075
DRD2	8.79	IC50	1.62	nM	CHEMBL_ACT_7667938
DRD3	8.49	Ki	3.2	nM	CHEMBL_ACT_25917661
DRD3	8.49	Ki	3.21	nM	CHEMBL_ACT_2601060
DRD2	8.42	AC50	3.8	nM	CHEMBL_ACT_25140030
HTR2A	8.41	AC50	3.9	nM	CHEMBL_ACT_25173513
HRH1	8.33	Ki	4.66	nM	CHEMBL_ACT_7667971
HTR2A	8.29	IC50	5.1	nM	CHEMBL_ACT_7670074
ADRA1A	8.19	Ki	6.5	nM	CHEMBL_ACT_25917700
DRD3	8.16	AC50	6.9	nM	CHEMBL_ACT_25193232
HTR7	8.1	Ki	8	nM	CHEMBL_ACT_25917689
SIGMAR1	8.07	Ki	8.57	nM	CHEMBL_ACT_7670089
P43140	8.02	Ki	9.58	nM	CHEMBL_ACT_7667863
ADRA1A	7.96	AC50	11.1	nM	CHEMBL_ACT_25137756
DRD1	7.96	Ki	11	nM	CHEMBL_ACT_7667937
ADRA2B	7.89	Ki	13	nM	CHEMBL_ACT_7667871
ADRA1D	7.8	Ki	16	nM	CHEMBL_ACT_7667867
P15823	7.72	Ki	19	nM	CHEMBL_ACT_7667865
SIGMAR1	7.7	IC50	20	nM	CHEMBL_ACT_7670088
DRD5	7.68	Ki	21	nM	CHEMBL_ACT_25917607
HRH1	7.68	Ki	21	nM	CHEMBL_ACT_25917716
DRD5	7.68	Ki	21	nM	CHEMBL_ACT_2601032
ADRA2C	7.66	Ki	22	nM	CHEMBL_ACT_7667873
DRD1	7.64	IC50	23	nM	CHEMBL_ACT_7667936
P43140	7.62	IC50	24	nM	CHEMBL_ACT_7667862

Target pathways

Aggregated over 7 target gene(s): HTR6, HTR7, DRD1, DRD2, DRD5, HRH1, HTR2A.

Top Reactome pathways

12 total, by targets touching each:

Pathway	Targets	Genes
G alpha (s) signalling events	4	DRD1, DRD5, HTR6, HTR7
Signal Transduction	3	HTR2A, HTR6, HTR7
Signaling by GPCR	3	HTR2A, HTR6, HTR7
Class A/1 (Rhodopsin-like receptors)	3	HTR2A, HTR6, HTR7
Amine ligand-binding receptors	3	HTR2A, HTR6, HTR7
GPCR downstream signalling	3	HTR2A, HTR6, HTR7
Dopamine receptors	3	DRD1, DRD2, DRD5
Serotonin receptors	3	HTR2A, HTR6, HTR7
GPCR ligand binding	3	HTR2A, HTR6, HTR7
G alpha (q) signalling events	2	HRH1, HTR2A
Histamine receptors	1	HRH1
RHOBTB3 ATPase cycle	1	HTR7

Dominant GO biological processes

GO term	Targets
signal transduction	7
G protein-coupled receptor signaling pathway	7
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	5
chemical synaptic transmission	5
response to cocaine	4
G protein-coupled serotonin receptor signaling pathway	3
temperature homeostasis	3
response to amphetamine	3
G protein-coupled dopamine receptor signaling pathway	3
memory	3
visual learning	3
response to xenobiotic stimulus	3
sensitization	3
behavioral response to cocaine	3
phospholipase C-activating dopamine receptor signaling pathway	3

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

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

Clinical trials

Total trials: 7.

Phase distribution

Phase	Trials
PHASE3	2
PHASE2	2
PHASE4	1
PHASE1/PHASE2	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT02307396	PHASE4	COMPLETED	Evaluation of the Necessity of Long-term Pharmacological Treatment With Antipsychotics in Schizophrenic Patients
NCT00161018	PHASE3	COMPLETED	New Antipsychotic Strategies: Quetiapine and Risperidone vs. Fluphenazine in Treatment Resistant Schizophrenia
NCT02374567	PHASE3	TERMINATED	Pharmacovigilance in Gerontopsychiatric Patients
NCT00335647	PHASE1/PHASE2	COMPLETED	Fluphenazine in Treating Patients With Refractory Advanced Multiple Myeloma
NCT00929578	PHASE2	COMPLETED	Fluphenazine Hydrochloride for Psoriasis
NCT02203786	PHASE2	COMPLETED	D1 and D2 Dopamine Receptors in Gambling and Amphetamine Reinforcement
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 or drug-level clinical/variant annotations in PharmGKB for this molecule.

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.

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

Molecule	Source	Status	Shared targets
BREXPIPRAZOLE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
OLANZAPINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
AMOXAPINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
CARIPRAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
CHLORPROMAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
DOXEPIN	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
HALOPERIDOL	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
IMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
KETOTIFEN	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
LOXAPINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
PROMAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
RISPERIDONE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
PENFLURIDOL	ChEMBL	Phase 2	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
RITANSERIN	ChEMBL	Phase 2	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR7
PRAMIPEXOLE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR7
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6
ASTEMIZOLE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
AZELASTINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
CYPROHEPTADINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
DIBENZEPIN	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
KETANSERIN	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
MAPROTILINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A, HTR6
METHYSERGIDE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
MIANSERIN	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
NEFAZODONE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
QUETIAPINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
TEGASEROD	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HTR2A, HTR6, HTR7
THIORIDAZINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
THIOTHIXENE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
ZIPRASIDONE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
LYSERGIDE	ChEMBL	Phase 2	DRD2, DRD5, HRH1, HTR2A, HTR6, HTR7
METERGOLINE	ChEMBL	Phase 2	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
NIGULDIPINE	ChEMBL	Phase 2	DRD1, DRD2, DRD5, HRH1, HTR6, HTR7
SPIPERONE	ChEMBL	Phase 2	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
Pyrazinamide	PubChem	Approved	DRD1, DRD2, HRH1, HTR2A, HTR6, HTR7
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6
TAMSULOSIN	ChEMBL + PubChem	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR7
AMIODARONE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6
APOMORPHINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A
ASENAPINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6
BENZTROPINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6
CABERGOLINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR2A
CARVEDILOL	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HTR2A, HTR6, HTR7
CHLORPROTHIXENE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, DRD5, HRH1, HTR6
CINACALCET	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR2A, HTR6, HTR7
CISAPRIDE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR7
CLEMASTINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6
EBASTINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6
FLUOXETINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6
HYDROXYZINE	ChEMBL	Phase 4 (approved)	DRD2, HRH1, HTR2A, HTR6, HTR7
ILOPERIDONE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6
LURASIDONE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR7
METHYLERGONOVINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	DRD1, DRD2, HRH1, HTR2A, HTR6