Fenfluramine

Summary

Fenfluramine (CHEMBL87493) is an approved small-molecule serotonin uptake inhibitor (ATC N03AX26) targeting TPH1 and TPH2; indicated across 5 conditions including epilepsy and obesity disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: N03AX26 (+1 more)
• Targets: 2 (TPH1, TPH2)
• Indications: 5 conditions
• Clinical trials: 14
• Chemistry: 231.26 Da · C12H16F3N

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL87493
Name	Fenfluramine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3337
ChEBI	CHEBI:5000
ATC	N03AX26, A08AA02
Molecular formula	C12H16F3N
Molecular weight	231.26
InChIKey	DBGIVFWFUFKIQN-UHFFFAOYSA-N

SMILES: CCNC(C)CC1=CC(=CC=C1)C(F)(F)F

IUPAC name: N-ethyl-1-[3-(trifluoromethyl)phenyl]propan-2-amine

ChEBI definition: A secondary amino compound that is 1-phenyl-propan-2-amine in which one of the meta-hydrogens is substituted by trifluoromethyl, and one of the hydrogens attached to the nitrogen is substituted by an ethyl group. It binds to the serotonin reuptake pump, causing inhbition of serotonin uptake and release of serotonin. The resulting increased levels of serotonin lead to greater serotonin receptor activation which in turn lead to enhancement of serotoninergic transmission in the centres of feeding behavior located in the hypothalamus. This suppresses the appetite for carbohydrates. Fenfluramine was used as the hydrochloride for treatment of diabetes and obesity. It was withdrawn worldwide after reports of heart valve disease and pulmonary hypertension.

Pharmacological roles (ChEBI): serotonin uptake inhibitor, serotonergic agonist, appetite depressant.

Also known as: Acino, Brabafen, Fenfluramin, Fenfluramina, Fenfluramine, J5.760F, Obedrex, Pesos, Phenfluramine, Ponderax pa, Rotondin, S-768

Parent form; salt/anhydrous children: CHEMBL2106217

Patent coverage: 5,102 distinct patent families (18,431 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 18,271 (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
TPH1	L-Tryptophan hydroxylase 1	Inhibition		0.3%	P17752
TPH2	L-Tryptophan hydroxylase 2	Inhibition			Q8IWU9

Broader ChEMBL bioactivity targets: 11 (assay-derived). Sample: Microtubule-associated protein tau, Prelamin-A/C, 5-hydroxytryptamine receptor 2B, Alpha-2C adrenergic receptor, 5-hydroxytryptamine receptor 2A, Sodium-dependent serotonin transporter, Alpha-1A adrenergic receptor, D(3) dopamine receptor, Kappa-type opioid receptor, Sodium-dependent serotonin transporter.

Bioactivity

ChEMBL activities: 10 potent at pChembl ≥ 5 of 13 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P31652	6.97	EC50	108	nM	CHEMBL_ACT_18042094
MAPT	6.9	Potency	125.9	nM	CHEMBL_ACT_4502642
Q01827	5.43	AC50	3714	nM	CHEMBL_ACT_25197373
HTR2B	5.36	AC50	4358	nM	CHEMBL_ACT_25164119
HTR2A	5.29	AC50	5100	nM	CHEMBL_ACT_25226358
ADRA1A	5.27	AC50	5386	nM	CHEMBL_ACT_25137941
HTR2A	5.17	AC50	6785	nM	CHEMBL_ACT_25173624
DRD3	5.1	AC50	8000	nM	CHEMBL_ACT_25193549
ADRA1A	5.04	AC50	9152	nM	CHEMBL_ACT_25138429
ADRA2C	5.03	AC50	9400	nM	CHEMBL_ACT_25147898

Target pathways

Aggregated over 2 target gene(s): TPH1, TPH2.

Top Reactome pathways

2 total, by targets touching each:

Pathway	Targets	Genes
Serotonin and melatonin biosynthesis	2	TPH1, TPH2
NGF-stimulated transcription	1	TPH1

Dominant GO biological processes

GO term	Targets
serotonin biosynthetic process	2
aromatic amino acid metabolic process	2
platelet degranulation	1
obsolete serotonin biosynthetic process from L-tryptophan	1
positive regulation of fat cell differentiation	1
bone remodeling	1
mammary gland alveolus development	1
regulation of hemostasis	1
phenol-containing compound biosynthetic process	1

Indications & clinical

Indications

5 indications (2 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
epilepsy	4	MONDO:0005027	EFO:0000474
obesity disorder	4	MONDO:0011122	EFO:0001073
Lennox-Gastaut syndrome	3	MONDO:0016532	MONDO:0016532
cocaine dependence	1	MONDO:0005186	EFO:0002610

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

Clinical trials

Total trials: 14.

Phase distribution

Phase	Trials
PHASE3	4
PHASE4	3
PHASE2	3
PHASE1	2
Not specified	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06598449	PHASE4	RECRUITING	Assessment of Safety of the Use of Fenfluramine in Children With Dravet Syndrome Under 24 Months of Age
NCT05026398	PHASE4	COMPLETED	Fenfluramine and Cognition
NCT05232630	PHASE4	UNKNOWN	Fenfluramine for the Treatment of Different Types of Developmental and Epileptic Encephalopathies: a Pilot Trial Exploring Epileptic and Non-epileptic Outcomes
NCT05064878	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study to Examine the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder.
NCT06118255	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Safety, Tolerability, and Pharmacokinetics of Fenfluramine (Hydrochloride) in Infants 1 Year to Less Than 2 Years of Age With Dravet Syndrome
NCT03355209	PHASE3	COMPLETED	A Study to Investigate the Efficacy and Safety of ZX008 (Fenfluramine Hydrochloride) as an Adjunctive Therapy in Children and Adults With Lennox-Gastaut Syndrome
NCT05560282	PHASE3	TERMINATED	Fenfluramine for Adult Dravet Patients
NCT04289467	PHASE2	RECRUITING	Treatment of Refractory Infantile Spasms With Fenfluramine
NCT00000506	PHASE2	COMPLETED	Cardiovascular System in Obesity: Effect of Treatment
NCT02655198	PHASE2	UNKNOWN	Add-on Therapy With Low Dose Fenfluramine in Lennox Gastaut Epilepsy
NCT00000313	PHASE1	TERMINATED	Predictive Values of Serotonergic Alterations for Outcome - 2
NCT03467113	PHASE1	COMPLETED	A Study to Assess the Safety and Tolerability of ZX008 in Children and Young Adults With Dravet Syndrome or Lennox Gastaut Syndrome Currently Taking Cannabidiol
NCT01296802	Not specified	COMPLETED	Investigation of Serotonin Neurotransmission in MDMA Users Using Combinated Dexfenfluramine Challenge and PET Imaging
NCT04437004	Not specified	APPROVED_FOR_MARKETING	Treatment of Dravet Syndrome With Fenfluramine (Expanded Access Protocol)

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.

4 molecules share ≥1 primary target. Top 4 by shared-target count:

Molecule	Source	Status	Shared targets
TELOTRISTAT	ChEMBL + PubChem	Phase 4 (approved)	TPH1, TPH2
TELOTRISTAT ETHYL	ChEMBL + PubChem	Phase 4 (approved)	TPH1, TPH2
RODATRISTAT	ChEMBL	Phase 2	TPH1, TPH2
TELOTRISTAT ETIPRATE	ChEMBL	Phase 4 (approved)	TPH1