Naphazoline
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Also known as NafazolinNafazolinaSID11112411SID26751615NAPHAZOLINE HYDROCHLORIDE
Summary
Naphazoline (CHEMBL761) is an approved small molecule (ATC R01AA08) targeting ADRA1A, ADRA2A, and ADRA2C; indicated across 8 conditions including eye allergy and atopic conjunctivitis.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: R01AA08 (+3 more)
- Targets: 3 (ADRA1A, ADRA2A, ADRA2C)
- Indications: 8 conditions
- Clinical trials: 6
- Chemistry: 210.27 Da · C14H14N2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL761 |
| Name | Naphazoline |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 4436 |
| ATC | R01AA08, S01GA51, S01GA01, R01AB02 |
| Molecular formula | C14H14N2 |
| Molecular weight | 210.27 |
| InChIKey | CNIIGCLFLJGOGP-UHFFFAOYSA-N |
SMILES: C1CN=C(N1)CC2=CC=CC3=CC=CC=C32
IUPAC name: 2-(naphthalen-1-ylmethyl)-4,5-dihydro-1H-imidazole
Also known as: Nafazolin, Nafazolina, Naphazoline, naphazoline, SID11112411, SID26751615, NAPHAZOLINE, NAPHAZOLINE HYDROCHLORIDE
Parent form; salt/anhydrous children: CHEMBL1706
Patent coverage: 3,741 distinct patent families (13,060 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 12,784 (98%) 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 |
|---|---|---|---|---|---|
| TAAR4P | Agonist | ||||
| ADRA1A | α1A-adrenoceptor | Full agonist | 6.5 | P35348 | |
| ADRA2A | α2A-adrenoceptor | Partial agonist | 7 | 0.1% | P08913 |
| ADRA2C | α2C-adrenoceptor | Agonist | 6.4 | 0% | P18825 |
Broader ChEMBL bioactivity targets: 15 (assay-derived). Sample: Microtubule-associated protein tau, Prelamin-A/C, Alpha-2A adrenergic receptor, Adrenergic receptor alpha-1, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Adrenergic receptor alpha-2, Adrenergic receptor alpha, 5-hydroxytryptamine receptor 1A, Alpha-1A adrenergic receptor.
Bioactivity
ChEMBL activities: 26 potent at pChembl ≥ 5 of 26 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| ADRA1A | 9.22 | AC50 | 0.6 | nM | CHEMBL_ACT_25230375 |
| ADRA1A | 8.85 | AC50 | 1.4 | nM | CHEMBL_ACT_25209089 |
| ADRA2C | 8.64 | Ki | 2.29 | nM | CHEMBL_ACT_15642440 |
| P19328 | 8.32 | IC50 | 4.8 | nM | CHEMBL_ACT_178928 |
| P15823 | 8.24 | Ki | 5.7 | nM | CHEMBL_ACT_14624391 |
| P19328 | 8.24 | Ki | 5.7 | nM | CHEMBL_ACT_523512 |
| ADRA2A | 8.06 | AC50 | 8.7 | nM | CHEMBL_ACT_25157098 |
| ADRA2A | 7.66 | AC50 | 22 | nM | CHEMBL_ACT_25157047 |
| ADRA2A | 7.37 | AC50 | 43 | nM | CHEMBL_ACT_25220562 |
| ADRA2C | 7.26 | EC50 | 54.95 | nM | CHEMBL_ACT_15642420 |
| ADRA1A | 7.2 | EC50 | 63.1 | nM | CHEMBL_ACT_209652 |
| ADRA1A | 7.2 | EC50 | 63.1 | nM | CHEMBL_ACT_580368 |
| HTR1A | 6.95 | AC50 | 113.6 | nM | CHEMBL_ACT_25165642 |
| NISCH | 6.92 | Ki | 121.6 | nM | CHEMBL_ACT_2564064 |
| NISCH | 6.92 | Ki | 121.6 | nM | CHEMBL_ACT_2564065 |
| ADRA2A | 6.85 | AC50 | 140 | nM | CHEMBL_ACT_25221768 |
| ADRA2B | 6.72 | AC50 | 190 | nM | CHEMBL_ACT_25144388 |
| Q4G017 | 6.61 | Ki | 245.5 | nM | CHEMBL_ACT_12459453 |
| ADRA2C | 6.48 | AC50 | 330 | nM | CHEMBL_ACT_25148588 |
| P15823 | 6.39 | IC50 | 410 | nM | CHEMBL_ACT_178927 |
| MAPT | 6.1 | Potency | 794.3 | nM | CHEMBL_ACT_4514977 |
| LMNA | 5.7 | Potency | 1995 | nM | CHEMBL_ACT_3652254 |
| MAPK1 | 5.4 | Potency | 3981 | nM | CHEMBL_ACT_4745674 |
| CYP2D6 | 5.1 | Potency | 7943 | nM | CHEMBL_ACT_4986063 |
| CYP2D6 | 5.1 | AC50 | 7943 | nM | CHEMBL_ACT_6019723 |
| OPRM1 | 5.08 | AC50 | 8367 | nM | CHEMBL_ACT_25158793 |
Target pathways
Aggregated over 3 target gene(s): ADRA1A, ADRA2A, ADRA2C.
Top Reactome pathways
21 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Signal Transduction | 3 | ADRA1A, ADRA2A, ADRA2C |
| Signaling by GPCR | 3 | ADRA1A, ADRA2A, ADRA2C |
| Class A/1 (Rhodopsin-like receptors) | 3 | ADRA1A, ADRA2A, ADRA2C |
| Amine ligand-binding receptors | 3 | ADRA1A, ADRA2A, ADRA2C |
| GPCR downstream signalling | 3 | ADRA1A, ADRA2A, ADRA2C |
| Adrenoceptors | 3 | ADRA1A, ADRA2A, ADRA2C |
| GPCR ligand binding | 3 | ADRA1A, ADRA2A, ADRA2C |
| Hemostasis | 2 | ADRA2A, ADRA2C |
| Metabolism | 2 | ADRA2A, ADRA2C |
| Integration of energy metabolism | 2 | ADRA2A, ADRA2C |
| Adrenaline signalling through Alpha-2 adrenergic receptor | 2 | ADRA2A, ADRA2C |
| Metabolism of proteins | 2 | ADRA2A, ADRA2C |
| Adrenaline,noradrenaline inhibits insulin secretion | 2 | ADRA2A, ADRA2C |
| G alpha (i) signalling events | 2 | ADRA2A, ADRA2C |
| G alpha (z) signalling events | 2 | ADRA2A, ADRA2C |
| Regulation of insulin secretion | 2 | ADRA2A, ADRA2C |
| Surfactant metabolism | 2 | ADRA2A, ADRA2C |
| Platelet activation, signaling and aggregation | 2 | ADRA2A, ADRA2C |
| Platelet Aggregation (Plug Formation) | 2 | ADRA2A, ADRA2C |
| G alpha (q) signalling events | 1 | ADRA1A |
| G alpha (12/13) signalling events | 1 | ADRA1A |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| signal transduction | 3 |
| G protein-coupled receptor signaling pathway | 3 |
| positive regulation of MAPK cascade | 3 |
| regulation of vasoconstriction | 3 |
| adrenergic receptor signaling pathway | 3 |
| cell-cell signaling | 2 |
| adenylate cyclase-activating adrenergic receptor signaling pathway | 2 |
| phospholipase C-activating adrenergic receptor signaling pathway | 2 |
| epidermal growth factor receptor signaling pathway | 2 |
| negative regulation of norepinephrine secretion | 2 |
| platelet activation | 2 |
| negative regulation of epinephrine secretion | 2 |
| negative regulation of insulin secretion | 2 |
| positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 2 |
| adenylate cyclase-inhibiting adrenergic receptor signaling pathway | 2 |
Indications & clinical
Indications
8 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 |
| atopic conjunctivitis | 3 | MONDO:0005642 | EFO:0007141 |
| common cold | 3 | MONDO:0005709 | EFO:0007214 |
| influenza | 3 | MONDO:0005812 | EFO:0007328 |
| respiratory system disorder | 3 | MONDO:0005087 | EFO:0000684 |
| neoplasm | 1 | MONDO:0005070 | EFO:0000616 |
2 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 6.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE3 | 3 |
| PHASE1 | 2 |
| PHASE4 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT01390961 | PHASE4 | UNKNOWN | Comparison of Tolerability Between Two Allergy Drops |
| 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. |
| NCT01533220 | PHASE3 | COMPLETED | Efficacy of Nasal Naphazoline Hydrocloride + Pheniramine Maleate + Panthenol Compared With Naphazoline Hydrocloride in the Symptomatic Control of Nasal Congestion and Nasopharyngeal |
| NCT03324113 | PHASE1 | COMPLETED | Evaluation of SAR408701 in Japanese Patients With Advanced Malignant Solid Tumors |
| NCT05470868 | PHASE1 | COMPLETED | Safety and Tolerability of PRO-185 |
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.
745 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| ACLIDINIUM BROMIDE | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CHENODIOL | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CLOFARABINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CLOZAPINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CRIZOTINIB | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| DESLORATADINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| DIHYDROERGOTAMINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| GENTIAN VIOLET | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| OLANZAPINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| OLODATEROL | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| PALIPERIDONE | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| Phenylpropanolamine | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| PRAMIPEXOLE | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| PROPOXYPHENE | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| PYRAZINAMIDE | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| TAMSULOSIN | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| TEGASEROD | ChEMBL + PubChem | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| ACETOPHENAZINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| ALFUZOSIN | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| AMLODIPINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| ANTAZOLINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| APOMORPHINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| APRACLONIDINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| ASENAPINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| ATRACURIUM | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| AZELASTINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| BAZEDOXIFENE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| BENPERIDOL | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| BITHIONOL | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| BOSUTINIB | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| BREXPIPRAZOLE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| BRIMONIDINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| BROMOCRIPTINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CABERGOLINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CABOZANTINIB | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CARIPRAZINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CHLORHEXIDINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CISAPRIDE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CLONIDINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| CYPROHEPTADINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| DARIFENACIN | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| DEXMEDETOMIDINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| DEXTROMETHORPHAN | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| DIETHYLSTILBESTROL | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| DOBUTAMINE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
| DOMPERIDONE | ChEMBL | Phase 4 (approved) | ADRA1A, ADRA2A, ADRA2C |
Related Atlas pages
- Genes: ADRA1A, ADRA2A, ADRA2C
- Diseases: eye allergy, atopic conjunctivitis, common cold, influenza, respiratory system disorder
- Drugs: Aclidinium Bromide, Chenodiol, Clofarabine, Clozapine, Crizotinib, Desloratadine, Dihydroergotamine, Olanzapine, Olodaterol, Paliperidone, Phenylpropanolamine, Pramipexole, Propoxyphene, Pyrazinamide, Tamsulosin, Tegaserod, Acetophenazine, Alfuzosin, Amitriptyline, Amlodipine, Amoxapine, Antazoline, Apomorphine, Apraclonidine, Aripiprazole, Asenapine, Astemizole, Atracurium, Azelastine, Bazedoxifene, Benfluorex, Benperidol, Benzbromarone, Benztropine, Bithionol, Bosutinib, Brexpiprazole, Brimonidine, Bromocriptine, Bromperidol, Cabergoline, Cabozantinib, Candesartan Cilexetil, Cariprazine, Carvedilol, Chlorhexidine, Chlorpromazine, Cinnarizine, Cisapride, Clemastine, Clomipramine, Clonidine, Cyproheptadine, Darifenacin, Dexmedetomidine, Dextromethorphan, Diethylstilbestrol, Dobutamine, Domperidone