Terfenadine

Summary

Terfenadine (CHEMBL17157) is an approved small molecule (ATC R06AX12) targeting CYP2J2, HRH1, and KCNH1; indicated across 12 conditions including allergic disease and chronic progressive multiple sclerosis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: R06AX12
• Targets: 4 (CYP2J2, HRH1, KCNH1…)
• Indications: 12 conditions
• Clinical trials: 28
• Chemistry: 471.7 Da · C32H41NO2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL17157
Name	Terfenadine
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	5405
ATC	R06AX12
Molecular formula	C32H41NO2
Molecular weight	471.7
InChIKey	GUGOEEXESWIERI-UHFFFAOYSA-N

SMILES: CC(C)(C)C1=CC=C(C=C1)C(CCCN2CCC(CC2)C(C3=CC=CC=C3)(C4=CC=CC=C4)O)O

IUPAC name: 1-(4-tert-butylphenyl)-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butan-1-ol

Also known as: Antihistamine, Histafen, Histafen 120, NSC-665802, NSC-758627, RMI 9918, RMI-9918, Seldane, Terfenadina, Terfenadine, Terfenor, Terfenor fte

Patent coverage: 7,224 distinct patent families (25,393 SureChEMBL compound mentions), from 1 matched compound structure(s). 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
CYP2J2	CYP2J2	Inhibition	5.09	0.2%	P51589
HRH1	H1 receptor	Antagonist	7.4	0%	P35367
KCNH1	Kv10.1		7.8	0.2%	O95259
KCNH2	Kv11.1		7.3	0.3%	Q12809

Broader ChEMBL bioactivity targets: 73 (assay-derived). Sample: Microtubule-associated protein tau, Ubiquitin carboxyl-terminal hydrolase 2, Nuclear receptor ROR-gamma, Prelamin-A/C, RecQ-like DNA helicase BLM, Ferritin light chain, Thrombopoietin, NPC intracellular cholesterol transporter 1, Geminin, Endonuclease 4.

Bioactivity

ChEMBL activities: 144 potent at pChembl ≥ 5 of 178 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
HRH1	9	IC50	1	nM	CHEMBL_ACT_15240062
P50637	9	IC50	1	nM	CHEMBL_ACT_25872928
HRH1	8.59	Ki	2.59	nM	CHEMBL_ACT_7818985
KCNH2	8.05	IC50	8.9	nM	CHEMBL_ACT_15257976
CYP2C19	8	Potency	10	nM	CHEMBL_ACT_4005995
CYP2C19	8	AC50	10	nM	CHEMBL_ACT_6039822
KCNH2	7.66	IC50	22	nM	CHEMBL_ACT_18243000
HRH1	7.66	IC50	22	nM	CHEMBL_ACT_7818984
KCNH2	7.64	IC50	23	nM	CHEMBL_ACT_29151152
KCNH2	7.57	IC50	27	nM	CHEMBL_ACT_29305215
KCNH2	7.52	IC50	30	nM	CHEMBL_ACT_2609309
KCNH2	7.52	IC50	30	nM	CHEMBL_ACT_2609320
HTR2B	7.52	Ki	30	nM	CHEMBL_ACT_7821085
P31389	7.45	Kd	35.48	nM	CHEMBL_ACT_1087774
HRH1	7.4	Ki	40	nM	CHEMBL_ACT_3001660
KCNH2	7.39	IC50	41	nM	CHEMBL_ACT_25451965
KCNH2	7.35	IC50	45	nM	CHEMBL_ACT_25902911
KCNH2	7.35	IC50	45	nM	CHEMBL_ACT_25943605
HTR2B	7.32	IC50	48	nM	CHEMBL_ACT_7821084
KCNH2	7.3	IC50	50	nM	CHEMBL_ACT_1449623
KCNH2	7.25	IC50	56	nM	CHEMBL_ACT_10883862
KCNH2	7.25	Ki	56	nM	CHEMBL_ACT_15240064
KCNH2	7.25	IC50	56	nM	CHEMBL_ACT_761333
KCNH2	7.25	IC50	56	nM	CHEMBL_ACT_931175
HRH1	7.24	Ki	58	nM	CHEMBL_ACT_931174
HTR2A	7.14	Ki	73	nM	CHEMBL_ACT_7821083
KCNH2	7.11	Ki	78	nM	CHEMBL_ACT_24513609
KCNH2	7.09	AC50	81	nM	CHEMBL_ACT_25117662
KCNH2	7.07	IC50	86	nM	CHEMBL_ACT_19109633
P31389	7.03	IC50	94	nM	CHEMBL_ACT_569390

Target pathways

Aggregated over 4 target gene(s): CYP2J2, HRH1, KCNH1, KCNH2.

Top Reactome pathways

11 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	2	KCNH1, KCNH2
Potassium Channels	2	KCNH1, KCNH2
Voltage gated Potassium channels	2	KCNH1, KCNH2
Fatty acids	1	CYP2J2
Xenobiotics	1	CYP2J2
Synthesis of epoxy (EET) and dihydroxyeicosatrienoic acids (DHET)	1	CYP2J2
Histamine receptors	1	HRH1
Muscle contraction	1	KCNH2
G alpha (q) signalling events	1	HRH1
Phase 3 - rapid repolarisation	1	KCNH2
Cardiac conduction	1	KCNH2

Dominant GO biological processes

GO term	Targets
potassium ion transport	2
regulation of membrane potential	2
potassium ion transmembrane transport	2
monoatomic ion transport	2
monoatomic ion transmembrane transport	2
transmembrane transport	2
obsolete organic acid metabolic process	1
fatty acid metabolic process	1
icosanoid metabolic process	1
xenobiotic metabolic process	1
regulation of heart contraction	1
epoxygenase P450 pathway	1
linoleic acid metabolic process	1
lipid metabolic process	1
arachidonate metabolic process	1

Indications & clinical

Indications

12 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
allergic disease	4	MONDO:0005271	MONDO:0005271
chronic progressive multiple sclerosis	3	MONDO:0005284	EFO:0003840
multiple sclerosis	3	MONDO:0005301	MONDO:0005301
hepatitis B virus infection	2	MONDO:0005344	EFO:0004197
hepatitis D virus infection	2	MONDO:0005789	EFO:0007304
diffuse large B-cell lymphoma	2	MONDO:0018905	EFO:0000403
asthma	2	MONDO:0004979	MONDO:0004979
breast neoplasm	1	MONDO:0021100	EFO:0003869
urinary bladder neoplasm	1	MONDO:0004987	EFO:0000294
esophageal squamous cell carcinoma	1	MONDO:0005580	EFO:0005922

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

Clinical trials

Total trials: 28.

Phase distribution

Phase	Trials
PHASE2	9
PHASE3	6
Not specified	6
PHASE1	4
PHASE4	1
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01382940	PHASE4	COMPLETED	A Study on The Safety of Administering Rituximab at A More Rapid Rate in Patients With Rheumatoid Arthritis
NCT04544436	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis (RMS)
NCT04548999	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Efficacy, Safety and Pharmacokinetics (PK) of a Higher Dose of Ocrelizumab in Adults With Primary Progressive Multiple Sclerosis (PPMS)
NCT00000363	PHASE3	COMPLETED	Acute Otitis Media: Adjuvant Therapy to Improve Outcome
NCT01380678	PHASE3	UNKNOWN	Intralesional Bevacizumab Injection on Primary Pterygium
NCT02688985	PHASE3	COMPLETED	Study to Explore the Mechanism of Action of Ocrelizumab and B-Cell Biology in Participants With Relapsing Multiple Sclerosis (RMS) or Primary Progressive Multiple Sclerosis (PPMS)
NCT06406153	PHASE3	COMPLETED	Efficacy and Safety of YW17 (Laronidase-CinnaGen) Compared to Aldurazyme® in MPS I Patients
NCT04743661	PHASE2	ACTIVE_NOT_RECRUITING	131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma
NCT05319730	PHASE1/PHASE2	RECRUITING	A Study to Evaluate Investigational Agents With or Without Pembrolizumab (MK-3475) in Participants With Advanced Esophageal Cancer Previously Exposed to Programmed Cell Death 1 Protein (PD-1)/ Programmed Cell Death Ligand 1 (PD-L1) Treatment (MK-3475-06B)
NCT00771875	PHASE2	COMPLETED	Randomized Trial for Mixed Acute Rejection
NCT01601522	PHASE2	COMPLETED	Peanut Allergy Oral Immunotherapy Desensitization
NCT02577029	PHASE2	TERMINATED	Study of ARC-520 With or Without Other Drugs Used in the Treatment of Chronic Chronic Hepatitis B Virus (HBV)
NCT02604199	PHASE2	TERMINATED	A Multi-dose Study of ARC-520 in Patients With Hepatitis B ’e’ Antigen (HBeAg) Negative, Chronic Hepatitis B Virus (HBV) Infection
NCT02604212	PHASE2	TERMINATED	A Multi-dose Study of ARC-520 in Patients With Hepatitis B ’e’ Antigen (HBeAg) Positive, Chronic Hepatitis B Virus Infection
NCT02738008	PHASE2	TERMINATED	Extension Study of the Safety and Efficacy of Multi-dose Intravenous ARC-520 in Patients With Chronic Hepatitis B (HBV) Infection
NCT03050866	PHASE2	UNKNOWN	Cabazitaxel in mCRPC Patients With AR-V7 Positive Circulating Tumor Cells (CTCs)
NCT04179461	PHASE2	COMPLETED	Personalized Treatment Algorithms for Difficult-to-treat Asthma
NCT01737931	PHASE1	COMPLETED	A Trial to Explore Symptomatic Therapy for Application Site Reaction to SPM962 in Healthy Subject
NCT02797522	PHASE1	TERMINATED	A Study of ARC-521 Injection in Normal Adult Volunteers and Patients With Chronic Hepatitis B (CHB)
NCT03258593	PHASE1	COMPLETED	Durvalumab and Vicineum in Subjects With High-Grade Non-Muscle-Invasive Bladder Cancer Previously Treated With Bacillus Calmette-Guerin (BCG)
NCT04568902	PHASE1	COMPLETED	Study of H3B-6545 in Japanese Women With Estrogen Receptor (ER)-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer
NCT05206227	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Histamine as a Molecular Transducer of Adaptation to Exercise
NCT04367883	Not specified	RECRUITING	Influenza Vaccination, ACEI and ARB in the Evolution of SARS-CoV2 Infection
NCT05504057	Not specified	RECRUITING	Antihistamines, Amantadine and Evolution of COVID-19
NCT07268248	Not specified	NOT_YET_RECRUITING	1-hour Premedication for Allergy Goal in Emergency: PAGE-1 Study
NCT01661777	Not specified	WITHDRAWN	Refractory Eustachian Tube Dysfunction: Are the Symptoms Related to Endolymphatic Hydrops
NCT04612803	Not specified	UNKNOWN	Prevalence of Antihistamine Responsive Irritable Bowel Syndrome With Diarrhea
NCT04935515	Not specified	COMPLETED	C Reactive Protein in Home Quarantined Coronavirus Disease 2019 (COVID -19) Patients.

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 3 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.

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

Molecule	Source	Status	Shared targets
HALOPERIDOL	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH1, KCNH2
Imipramine	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH1, KCNH2
Amiodarone	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
Clotrimazole	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
CLOZAPINE	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
Cyclobenzaprine	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
Diphenhydramine	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
Domperidone	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
Erythromycin	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
Fluoxetine	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
Nortriptyline	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
PERPHENAZINE	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
Pimozide	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
Pitolisant	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
Thioridazine	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
BEPRIDIL	ChEMBL	Phase 4 (approved)	CYP2J2, HRH1, KCNH2
FLUNARIZINE	ChEMBL	Phase 2	CYP2J2, HRH1, KCNH2
ACLIDINIUM BROMIDE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, KCNH2
Afatinib	ChEMBL + PubChem	Phase 4 (approved)	HRH1, KCNH2
Albendazole	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Almotriptan	ChEMBL + PubChem	Phase 4 (approved)	HRH1, KCNH2
CHLORPROMAZINE	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1
Clomiphene	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Crizotinib	ChEMBL + PubChem	Phase 4 (approved)	HRH1, KCNH2
dacomitinib	ChEMBL + PubChem	Phase 4 (approved)	HRH1, KCNH2
Desipramine	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1
DESLORATADINE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, KCNH2
Dextromethorphan	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
DIHYDROERGOTAMINE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, KCNH2
Diltiazem	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Dofetilide	ChEMBL + PubChem	Phase 4 (approved)	KCNH1, KCNH2
Dronedarone	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Fexofenadine	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1
Flecainide	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Isradipine	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Loratadine	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1
Methadone	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Mexiletine	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
NICARDIPINE	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
NIFEDIPINE	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Olodaterol	ChEMBL + PubChem	Phase 4 (approved)	HRH1, KCNH2
Orphenadrine	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1
PALIPERIDONE	ChEMBL + PubChem	Phase 4 (approved)	HRH1, KCNH2
PAROXETINE	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Propafenone	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Propoxyphene	ChEMBL + PubChem	Phase 4 (approved)	HRH1, KCNH2
Propranolol	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Quinidine	ChEMBL + PubChem	Phase 4 (approved)	KCNH1, KCNH2
Ranolazine	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
rifampin	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1
SERTRALINE	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, HRH1
Tazemetostat	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Telotristat Ethyl	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
VERAPAMIL	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
Vorapaxar	ChEMBL + PubChem	Phase 4 (approved)	CYP2J2, KCNH2
ABEMACICLIB	ChEMBL	Phase 4 (approved)	HRH1, KCNH2
ACETOPHENAZINE	ChEMBL	Phase 4 (approved)	HRH1, KCNH2
AMISULPRIDE	ChEMBL	Phase 4 (approved)	HRH1, KCNH2
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	HRH1, KCNH2
AMODIAQUINE	ChEMBL	Phase 4 (approved)	CYP2J2, KCNH2