Ketotifen
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Also known as (r)-ketotifenKetotifeneKetotifenoSID11111350SID11111351SID11113338SID26751502SID90341121SID104171180SID50100258SID50104048SID144203727SID170465378
Summary
Ketotifen (CHEMBL534) is an approved small-molecule H1-receptor antagonist (ATC R06AX17) targeting HRH1; indicated across 10 conditions including eye allergy and allergic disease.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: R06AX17 (+1 more)
- Targets: 1 (HRH1)
- Indications: 10 conditions
- Clinical trials: 18
- Chemistry: 309.4 Da · C19H19NOS
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL534 |
| Name | Ketotifen |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 3827 |
| ChEBI | CHEBI:92511 |
| ATC | R06AX17, S01GX08 |
| Molecular formula | C19H19NOS |
| Molecular weight | 309.4 |
| InChIKey | ZCVMWBYGMWKGHF-UHFFFAOYSA-N |
SMILES: CN1CCC(=C2C3=C(C(=O)CC4=CC=CC=C42)SC=C3)CC1
IUPAC name: 2-(1-methylpiperidin-4-ylidene)-6-thiatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-8-one
ChEBI definition: An organic heterotricyclic compound that is 4,9-dihydro-10H-benzo[4,5]cyclohepta[1,2-b]thiophen-10-one which is substituted at position 4 by a 1-methylpiperidin-4-ylidene group. A blocker of histamine H1 receptors with a stabilising action on mast cells, it is used (usually as its hydrogen fumarate salt) for the treatment of asthma, where it may take several weeks to exert its full effect.
Pharmacological roles (ChEBI): H1-receptor antagonist, anti-asthmatic drug.
Also known as: (r)-ketotifen, Ketotifen, Ketotifene, Ketotifeno, SID11111350, SID11111351, SID11113338, SID26751502, SID90341121, ketotifen, SID104171180, SID50100258
Parent form; salt/anhydrous children: CHEMBL1633
Patent coverage: 5,600 distinct patent families (21,815 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 21,782 (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 |
|---|---|---|---|---|---|
| HRH1 | H1 receptor | Antagonist | 8.6 | 0% | P35367 |
Broader ChEMBL bioactivity targets: 34 (assay-derived). Sample: Prelamin-A/C, Inositol monophosphatase 1, Muscarinic acetylcholine receptor M4, 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, 5-hydroxytryptamine receptor 3A, Alpha-2C adrenergic receptor, Histamine H2 receptor, Alpha-2B adrenergic receptor, Thyrotropin receptor.
Bioactivity
ChEMBL activities: 77 potent at pChembl ≥ 5 of 87 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| HRH1 | 9.86 | Ki | 0.14 | nM | CHEMBL_ACT_7748425 |
| HRH1 | 9.8 | Ki | 0.16 | nM | CHEMBL_ACT_3562033 |
| P31389 | 9.51 | Ki | 0.31 | nM | CHEMBL_ACT_1262101 |
| P31389 | 9.5 | Kd | 0.32 | nM | CHEMBL_ACT_642591 |
| P31389 | 9.5 | Kd | 0.32 | nM | CHEMBL_ACT_950450 |
| HRH1 | 9 | IC50 | 1 | nM | CHEMBL_ACT_6198202 |
| HRH1 | 8.93 | IC50 | 1.19 | nM | CHEMBL_ACT_7748424 |
| LMNA | 8.7 | Potency | 2 | nM | CHEMBL_ACT_3645347 |
| HTR2A | 8.05 | Ki | 8.98 | nM | CHEMBL_ACT_7750545 |
| HTR2A | 7.8 | Ki | 15.85 | nM | CHEMBL_ACT_3561995 |
| CHRM3 | 7.75 | AC50 | 18 | nM | CHEMBL_ACT_25136379 |
| HTR2B | 7.54 | Ki | 29 | nM | CHEMBL_ACT_7750547 |
| HTR2A | 7.51 | IC50 | 31 | nM | CHEMBL_ACT_7750544 |
| HTR2B | 7.5 | Ki | 31.62 | nM | CHEMBL_ACT_3561957 |
| HTR2A | 7.49 | AC50 | 32.1 | nM | CHEMBL_ACT_25173499 |
| HTR2B | 7.48 | AC50 | 32.8 | nM | CHEMBL_ACT_25164021 |
| HTR2B | 7.34 | IC50 | 46 | nM | CHEMBL_ACT_7750546 |
| HTR2C | 7.08 | Ki | 84 | nM | CHEMBL_ACT_7750549 |
| HTR2B | 7.05 | AC50 | 90 | nM | CHEMBL_ACT_25227220 |
| CHRM4 | 6.85 | Ki | 141 | nM | CHEMBL_ACT_7748459 |
| HTR2C | 6.8 | IC50 | 160 | nM | CHEMBL_ACT_7750548 |
| P08482 | 6.75 | Potency | 177.8 | nM | CHEMBL_ACT_4803430 |
| HTR2C | 6.7 | Ki | 199.5 | nM | CHEMBL_ACT_3561919 |
| CHRM1 | 6.57 | Ki | 268 | nM | CHEMBL_ACT_7748453 |
| CHRM5 | 6.57 | Ki | 269 | nM | CHEMBL_ACT_7748461 |
| CHRM2 | 6.53 | Ki | 298 | nM | CHEMBL_ACT_7748455 |
| ADRA2B | 6.49 | Ki | 324 | nM | CHEMBL_ACT_7780442 |
| HTR2A | 6.46 | AC50 | 344.8 | nM | CHEMBL_ACT_25224873 |
| CHRM5 | 6.43 | IC50 | 374 | nM | CHEMBL_ACT_7748460 |
| P15917 | 6.4 | Potency | 398.1 | nM | CHEMBL_ACT_4675336 |
Target pathways
Aggregated over 1 target gene(s): HRH1.
Top Reactome pathways
2 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Histamine receptors | 1 | HRH1 |
| G alpha (q) signalling events | 1 | HRH1 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| inflammatory response | 1 |
| G protein-coupled receptor signaling pathway | 1 |
| G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | 1 |
| phospholipase C-activating G protein-coupled receptor signaling pathway | 1 |
| chemical synaptic transmission | 1 |
| memory | 1 |
| visual learning | 1 |
| regulation of vascular permeability | 1 |
| positive regulation of vasoconstriction | 1 |
| regulation of synaptic plasticity | 1 |
| cellular response to histamine | 1 |
| signal transduction | 1 |
| phospholipase C-activating serotonin receptor signaling pathway | 1 |
Indications & clinical
Indications
10 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 |
|---|---|---|---|
| eye allergy | 4 | MONDO:0005551 | EFO:0005751 |
| allergic disease | 4 | MONDO:0005271 | MONDO:0005271 |
| fibromyalgia | 3 | MONDO:0005546 | EFO:0005687 |
| atopic conjunctivitis | 3 | MONDO:0005642 | EFO:0007141 |
| perennial allergic rhinitis | 3 | MONDO:0024332 | EFO:1001417 |
| dyspepsia | 3 | MONDO:0002268 | EFO:0008533 |
| severe acute respiratory syndrome | 3 | MONDO:0005091 | MONDO:0100096 |
| peripheral nervous system disorder | 3 | MONDO:0003620 | EFO:0004149 |
2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 18.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE3 | 8 |
| PHASE2 | 5 |
| PHASE4 | 3 |
| Not specified | 2 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00133627 | PHASE4 | COMPLETED | Ketotifen Ophthalmic Solution With Emedastine in Patients With Seasonal Allergic Conjunctivitis |
| NCT02673840 | PHASE4 | UNKNOWN | Ketotifen as a Treatment for Vascular Leakage During Dengue Fever |
| NCT05616442 | PHASE4 | COMPLETED | Ketotifen in Non-Alcoholic Fatty Liver Disease Patients |
| NCT02484248 | PHASE3 | RECRUITING | Ketotifen for Children With Functional Dyspepsia in Association With Duodenal Eosinophilia |
| NCT05624138 | PHASE3 | RECRUITING | The Possible Protective Role of Ketotifen Against Oxaliplatin Induced Peripheral Neuropathy |
| NCT00569777 | PHASE3 | COMPLETED | Safety Study of a Contact Lens With Ketotifen in Healthy, Normal Volunteers |
| NCT00639587 | PHASE3 | COMPLETED | Efficacy and Safety of Cetirizine Tablets Versus Ketotifen Dry Syrup in Children With Perennial Allergic Rhinitis |
| NCT00769886 | PHASE3 | COMPLETED | Ketotifen/Naphazoline Ophthalmic Solution in the Conjunctival Allergen Challenge Model of Allergic Conjunctivitis. |
| NCT00770133 | PHASE3 | COMPLETED | Ketotifen/Naphazoline Ophthalmic Solution in the Conjunctival Allergen Challenge Model of Acute Allergic Conjunctivitis. |
| NCT01553318 | PHASE3 | COMPLETED | Novel Use of (Oral) Ketotifen for the Treatment of Fibromyalgia: A Pilot Study |
| NCT05007522 | PHASE3 | COMPLETED | Ketotifen and Indomethacin Combination Treatment Clinical Trial for COVID-19 |
| NCT07526558 | PHASE2 | NOT_YET_RECRUITING | Mast Cell Treatment in Post-tick Bite Illness (PTBI) |
| NCT00375596 | PHASE2 | WITHDRAWN | A Study Of The Safety And Effectiveness Of A New Treatment For Allergic Conjunctivitis |
| NCT00836485 | PHASE2 | COMPLETED | Evaluation of the Safety and Efficacy of Ketotifen 4.0% Patch as Compared to Placebo Patch, Olopatadine 0.2% Ophthalmic Solution, and Artificial Tears in the Conjunctival Allergen Challenge (CAC) Model of Acute Allergic Conjunctivitis |
| NCT01625715 | PHASE2 | UNKNOWN | Pilot Study to Evaluate the Effect of Ketotifen on the Adverse Events Associated With Peanut Desensitization |
| NCT01902017 | PHASE2 | COMPLETED | Investigations of Mechanisms and Treatment in Post-traumatic Joint Contractures |
| NCT04399148 | Not specified | COMPLETED | Influence of Antipruritics on the Dermal Blood Flow Response to Histamine, Cinnamaldehyde and Capsaicin. |
| NCT04435028 | Not specified | COMPLETED | Ketotifen: as a Cardioprotective Agent in Breast Cancer Patients Receiving Anthracycline-containing Chemotherapy |
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.
295 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| ACLIDINIUM BROMIDE | ChEMBL + PubChem | Phase 4 (approved) | HRH1 |
| DESLORATADINE | ChEMBL + PubChem | Phase 4 (approved) | HRH1 |
| DIHYDROERGOTAMINE | ChEMBL + PubChem | Phase 4 (approved) | HRH1 |
| PALIPERIDONE | ChEMBL + PubChem | Phase 4 (approved) | HRH1 |
| PRAMIPEXOLE | ChEMBL + PubChem | Phase 4 (approved) | HRH1 |
| ABEMACICLIB | ChEMBL | Phase 4 (approved) | HRH1 |
| ACETOPHENAZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| ACRIVASTINE | ChEMBL | Phase 4 (approved) | HRH1 |
| AMIODARONE | ChEMBL | Phase 4 (approved) | HRH1 |
| AMISULPRIDE | ChEMBL | Phase 4 (approved) | HRH1 |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | HRH1 |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | HRH1 |
| AMSACRINE | ChEMBL | Phase 4 (approved) | HRH1 |
| ANTAZOLINE | ChEMBL | Phase 4 (approved) | HRH1 |
| APOMORPHINE | ChEMBL | Phase 4 (approved) | HRH1 |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | HRH1 |
| ASENAPINE | ChEMBL | Phase 4 (approved) | HRH1 |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | HRH1 |
| ATOMOXETINE | ChEMBL | Phase 4 (approved) | HRH1 |
| AZATADINE | ChEMBL | Phase 4 (approved) | HRH1 |
| AZELASTINE | ChEMBL | Phase 4 (approved) | HRH1 |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | HRH1 |
| BENPERIDOL | ChEMBL | Phase 4 (approved) | HRH1 |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | HRH1 |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | HRH1 |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | HRH1 |
| BETAMETHASONE PHOSPHORIC ACID | ChEMBL | Phase 4 (approved) | HRH1 |
| BIPERIDEN | ChEMBL | Phase 4 (approved) | HRH1 |
| BREXPIPRAZOLE | ChEMBL | Phase 4 (approved) | HRH1 |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | HRH1 |
| BROMPHENIRAMINE | ChEMBL | Phase 4 (approved) | HRH1 |
| BUCLIZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| BUPROPION | ChEMBL | Phase 4 (approved) | HRH1 |
| BUSPIRONE | ChEMBL | Phase 4 (approved) | HRH1 |
| BUTRIPTYLINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CABERGOLINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | HRH1 |
| CAPTOPRIL | ChEMBL | Phase 4 (approved) | HRH1 |
| CARBINOXAMINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CARIPRAZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CETIRIZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CHLORDIAZEPOXIDE | ChEMBL | Phase 4 (approved) | HRH1 |
| CHLORPHENIRAMINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CHLORPHENTERMINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CHLORPROTHIXENE | ChEMBL | Phase 4 (approved) | HRH1 |
| CINACALCET | ChEMBL | Phase 4 (approved) | HRH1 |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CISAPRIDE | ChEMBL | Phase 4 (approved) | HRH1 |
| CITALOPRAM | ChEMBL | Phase 4 (approved) | HRH1 |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CLOFAZIMINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | HRH1 |
| CLOZAPINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CYCLIZINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CYCLOBENZAPRINE | ChEMBL | Phase 4 (approved) | HRH1 |
| CYPROHEPTADINE | ChEMBL | Phase 4 (approved) | HRH1 |
| DAUNORUBICIN | ChEMBL | Phase 4 (approved) | HRH1 |
| DESIPRAMINE | ChEMBL | Phase 4 (approved) | HRH1 |
Related Atlas pages
- Genes: HRH1
- Diseases: eye allergy, allergic disease, fibromyalgia, atopic conjunctivitis, perennial allergic rhinitis, dyspepsia, severe acute respiratory syndrome, peripheral nervous system disorder
- Drugs: Aclidinium Bromide, Desloratadine, Dihydroergotamine, Paliperidone, Pramipexole, Abemaciclib, Acetophenazine, Acrivastine, Amiodarone, Amisulpride, Amitriptyline, Amoxapine, Amsacrine, Antazoline, Apomorphine, Aripiprazole, Asenapine, Astemizole, Atomoxetine, Azatadine, Azelastine, Benfluorex, Benperidol, Benzbromarone, Benztropine, Bepridil, Betamethasone Phosphoric Acid, Biperiden, Brexpiprazole, Bromperidol, Brompheniramine, Buclizine, Bupropion, Buspirone, Butriptyline, Cabergoline, Candesartan Cilexetil, Captopril, Carbinoxamine, Cariprazine, Cetirizine, Chlordiazepoxide, Chlorpheniramine, Chlorphentermine, Chlorpromazine, Chlorprothixene, Cinacalcet, Cinnarizine, Cisapride, Citalopram, Clemastine, Clofazimine, Clomipramine, Clotrimazole, Clozapine, Cyclizine, Cyclobenzaprine, Cyproheptadine, Daunorubicin, Desipramine