Azelastine

drug
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Also known as AzelastinaNSC-758971rac-AzelastineAzelastineAstelinOptivar

Summary

Azelastine (CHEMBL639) is an approved small-molecule H1-receptor antagonist (ATC R01AC03) targeting HRH1; indicated across 6 conditions including eye allergy and allergic disease.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: R01AC03 (+2 more)
  • Targets: 1 (HRH1)
  • Indications: 6 conditions
  • Clinical trials: 27
  • Chemistry: 381.9 Da · C22H24ClN3O

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL639
NameAzelastine
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID2267
ChEBICHEBI:2950
ATCR01AC03, R06AX19, S01GX07
Molecular formulaC22H24ClN3O
Molecular weight381.9
InChIKeyMBUVEWMHONZEQD-UHFFFAOYSA-N

SMILES: CN1CCCC(CC1)N2C(=O)C3=CC=CC=C3C(=N2)CC4=CC=C(C=C4)Cl

IUPAC name: 4-[(4-chlorophenyl)methyl]-2-(1-methylazepan-4-yl)phthalazin-1-one

ChEBI definition: A phthalazine compound having an oxo substituent at the 1-position, a 1-methylazepan-4-yl group at the 2-position and a 4-chlorobenzyl substituent at the 4-position.

Pharmacological roles (ChEBI): H1-receptor antagonist, anti-allergic agent, anti-asthmatic drug, bronchodilator agent, platelet aggregation inhibitor, EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor.

Also known as: Azelastina, Azelastine, NSC-758971, rac-Azelastine, azelastine, AZELASTINE, Azelastine; Astelin, Optivar

Parent form; salt/anhydrous children: CHEMBL1200809

Patent coverage: 4,301 distinct patent families (16,805 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 16,664 (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).

GeneTargetActionpAffinityCancer dependencyUniProt
HRH1H1 receptorAntagonist8.90%P35367

Broader ChEMBL bioactivity targets: 28 (assay-derived). Sample: 5-hydroxytryptamine receptor 2B, Alpha-2A adrenergic receptor, Neuronal acetylcholine receptor subunit alpha-4, 5-hydroxytryptamine receptor 3A, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Muscarinic acetylcholine receptor M2, Beta-1 adrenergic receptor, Muscarinic acetylcholine receptor M1, Sodium-dependent noradrenaline transporter.

Bioactivity

ChEMBL activities: 47 potent at pChembl ≥ 5 of 57 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
HRH19.7Kd0.2nMCHEMBL_ACT_12037515
HRH19.7Kd0.2nMCHEMBL_ACT_16812248
HRH19.7Kd0.2nMCHEMBL_ACT_18221313
HRH19.7Kd0.2nMCHEMBL_ACT_25101033
HRH19.7Kd0.2nMCHEMBL_ACT_6175539
HRH18.92Ki1.2nMCHEMBL_ACT_12037516
HRH18.92Ki1.2nMCHEMBL_ACT_16812132
HRH18.9Ki1.26nMCHEMBL_ACT_25101076
HRH18.9Ki1.26nMCHEMBL_ACT_6175677
HTR2B7.7Ki19.95nMCHEMBL_ACT_18221379
HRH17.62AC5024nMCHEMBL_ACT_25212184
ADRA1B7.3Ki50.12nMCHEMBL_ACT_12037464
ADRA1A7.3Ki50.12nMCHEMBL_ACT_12037496
ADRA1A7.3Ki50.12nMCHEMBL_ACT_16812166
ADRA1B7.3Ki50.12nMCHEMBL_ACT_16812183
P431407.3Ki50.12nMCHEMBL_ACT_18221383
ADRA1A7.3Ki50.12nMCHEMBL_ACT_25101088
ADRA1B7.3Ki50.12nMCHEMBL_ACT_25101100
ADRA1B7.3Ki50.12nMCHEMBL_ACT_6175568
ADRA1A7.3Ki50.12nMCHEMBL_ACT_6175604
KCNH27IC50100nMCHEMBL_ACT_12037489
KCNH27IC50100nMCHEMBL_ACT_16812217
KCNH27IC50100nMCHEMBL_ACT_18221256
KCNH27IC50100nMCHEMBL_ACT_25101123
KCNH27IC50100nMCHEMBL_ACT_25101147
KCNH27IC50100nMCHEMBL_ACT_6175529
HRH36.83Ki147.9nMCHEMBL_ACT_12037424
HRH36.83Ki147.9nMCHEMBL_ACT_16812149
HRH36.8Ki158.5nMCHEMBL_ACT_6175636
P0DTC26.59Kd258nMCHEMBL_ACT_29077440

Target pathways

Aggregated over 1 target gene(s): HRH1.

Top Reactome pathways

2 total, by targets touching each:

PathwayTargetsGenes
Histamine receptors1HRH1
G alpha (q) signalling events1HRH1

Dominant GO biological processes

GO termTargets
inflammatory response1
G protein-coupled receptor signaling pathway1
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger1
phospholipase C-activating G protein-coupled receptor signaling pathway1
chemical synaptic transmission1
memory1
visual learning1
regulation of vascular permeability1
positive regulation of vasoconstriction1
regulation of synaptic plasticity1
cellular response to histamine1
signal transduction1
phospholipase C-activating serotonin receptor signaling pathway1

Indications & clinical

Indications

6 indications (3 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).

IndicationTrial phaseMONDOEFO
eye allergy4MONDO:0005551EFO:0005751
allergic disease4MONDO:0005271MONDO:0005271
seasonal allergic rhinitis3MONDO:0005324EFO:0003956
allergic rhinitis3MONDO:0011786EFO:0005854
perennial allergic rhinitis3MONDO:0024332EFO:1001417

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

Clinical trials

Total trials: 27.

Phase distribution

PhaseTrials
PHASE410
PHASE39
PHASE24
PHASE13
Not specified1

Top trials by phase / activity

NCTPhaseStatusTitle
NCT05626621PHASE4RECRUITINGEfficacy of Azelastine and Mometasone Irrigation in Comparison to Nasal Sprays in Patients With Chronic Rhinitis
NCT00561717PHASE4COMPLETEDA Randomized, Placebo Controlled Study to Determine the Efficacy and Speed of a Nasal Spray in Allergen Induced Seasonal Allergic Rhinitis
NCT00806754PHASE4COMPLETEDInvestigation of the Efficacy and Safety of Concomitant Administration of Ciclesonide Nasal Spray and Azelastine Nasal Spray in Patients (18 Years or Older) With Perennial Allergic Rhinitis (PAR) Not Adequately Controlled on an Intranasal Corticosteroid or Antihistamine Monotherapy (BY9010/M1-490)
NCT00845195PHASE4COMPLETEDComparison of Seasonal Allergic Rhinitis Treatment With 2 Antihistamines Used in Combination With Intranasal Corticosteroid
NCT00845598PHASE4WITHDRAWNAzelastine Fluticasone Combination vs. Fluticasone
NCT00979615PHASE4COMPLETEDSafety and Efficacy of Olopatadine 0.6% and Azelastine 137 Mcg in Vasomotor Rhinitis
NCT02238353PHASE4UNKNOWNAZELASTINE/FLUTICASONE (AZE/FLU) Nasal Spray on Symptom Control, Nasal Mediators and Nasal Hyperresponsiveness in Allergic Rhinitis (AR)
NCT03004131PHASE4COMPLETEDMP-AzeFlu Allergen Chamber - Onset of Action Study
NCT04601324PHASE4WITHDRAWNAllergic Rhinitis Combination Pharmacotherapy Efficacy Study
NCT06800274PHASE4COMPLETEDClinical and Biological Evaluation of NAAGA Versus Azelastine Eye Drops in Allergic Subjects With Tear Film Dysfunction
NCT01018862PHASE3COMPLETEDA Study to Evaluate the Safety and Efficacy of a Nasal Spray to Treat Children With Perennial Allergic Rhinitis
NCT01368445PHASE3COMPLETEDA Study to Evaluate the Safety and Efficacy of a Nasal Spray to Treat Seasonal Allergies
NCT01915823PHASE3COMPLETEDSafety and Efficacy Trial of Dymista Nasal Spray in Children Ages 4 to 11 With Seasonal Allergic Rhinitis (SAR)
NCT02249663PHASE3UNKNOWNClinical Equivalence of Azelastine Hydrochloride and Fluticasone Propionate, 137/50 mcg Nasal Spray to Dymista™
NCT03599791PHASE3COMPLETEDDYmista NAsal Spray in CHInese Patients
NCT04264637PHASE3COMPLETEDStudy to Find Out How Long it Takes Azelastine Hydrochloride 0.15% Nasal Spray to Relieve Symptoms in Patients Suffering From Allergic Rhinitis
NCT05311475PHASE3COMPLETEDProspective, Randomized, Multinational, Multicenter, Double-blind, Placebo and Active Controlled Trial in 4 Parallel-groups of Patients Suffering From Seasonal Allergic Rhinitis
NCT05590598PHASE3COMPLETEDEfficacy and Safety of Azelastine +Mometasone , Nasal Spray, 140 mcg + 50 mcg, (Sandoz d.d., Slovenia) and Momat Rino Advance, Nasal Spray, 140 mcg + 50 mcg, (Glenmark, India) Administered as a Monotherapy to Patients With Seasonal Allergic Rhinitis.
NCT06212973PHASE3COMPLETEDA Study to Evaluate the Efficacy and Safety of Epinastine Hydrochloride Eye Drops in the Treatment of Chinese Seasonal Allergic Conjunctivitis Patients
NCT00940953PHASE2COMPLETEDCompare Captisol-Enabled (CE) Budesonide + Azelastine Nasal Solution and Rhinocort Aqua + Astelin in an Environmental Exposure Chamber (EEC) Study of Allergic Rhinitis
NCT01382654PHASE2COMPLETEDTwo Formulations and Concentrations of Epinastine Nasal Spray Versus Azelastine Nasal Solution for Allergic Rhinitis
NCT02279563PHASE2UNKNOWNA Study Comparing the Bioequivalence of Azelastine Hydrochloride and Fluticasone Propionate Nasal Spray (Apotex, Inc.) to That of Dymista™ Nasal Spray (Meda Pharmaceuticals, Inc.) in the Treatment of Seasonal Allergic Rhinitis
NCT06051786PHASE2COMPLETEDA Study to Evaluate the Safety and Effectiveness of a Nasal Spray to Treat Perennial Allergic Rhinitis
NCT01190852PHASE1COMPLETEDSingle Dose Pharmacokinetics of Intranasal Azelastine Delivered by a Fixed Combination With Fluticasone in Comparison to Azelastine Nasal Sprays
NCT01194622PHASE1COMPLETEDSingle Dose Pharmacokinetics of Intranasal Fluticasone Delivered by a Fixed Combination With Azelastine (MP29 02) in Comparison to Two Different Fluticasone Nasal Sprays
NCT05887843PHASE1TERMINATEDStudy to Compare the Pharmacokinetics of Fixed-Dose Combination of Mometasone + Azelastine Nasal Spray to Mometasone and Azelastine Nasal Sprays in Adolescents and Young Adults With Seasonal Allergic Rhinitis
NCT04561687Not specifiedUNKNOWNComparison of Montelukast and Azelastine in Treatment of Moderate to Severe Allergic Rhinitis

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.

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:

MoleculeSourceStatusShared targets
ACLIDINIUM BROMIDEChEMBL + PubChemPhase 4 (approved)HRH1
DESLORATADINEChEMBL + PubChemPhase 4 (approved)HRH1
DIHYDROERGOTAMINEChEMBL + PubChemPhase 4 (approved)HRH1
PALIPERIDONEChEMBL + PubChemPhase 4 (approved)HRH1
PRAMIPEXOLEChEMBL + PubChemPhase 4 (approved)HRH1
ABEMACICLIBChEMBLPhase 4 (approved)HRH1
ACETOPHENAZINEChEMBLPhase 4 (approved)HRH1
ACRIVASTINEChEMBLPhase 4 (approved)HRH1
AMIODARONEChEMBLPhase 4 (approved)HRH1
AMISULPRIDEChEMBLPhase 4 (approved)HRH1
AMITRIPTYLINEChEMBLPhase 4 (approved)HRH1
AMOXAPINEChEMBLPhase 4 (approved)HRH1
AMSACRINEChEMBLPhase 4 (approved)HRH1
ANTAZOLINEChEMBLPhase 4 (approved)HRH1
APOMORPHINEChEMBLPhase 4 (approved)HRH1
ARIPIPRAZOLEChEMBLPhase 4 (approved)HRH1
ASENAPINEChEMBLPhase 4 (approved)HRH1
ASTEMIZOLEChEMBLPhase 4 (approved)HRH1
ATOMOXETINEChEMBLPhase 4 (approved)HRH1
AZATADINEChEMBLPhase 4 (approved)HRH1
BENFLUOREXChEMBLPhase 4 (approved)HRH1
BENPERIDOLChEMBLPhase 4 (approved)HRH1
BENZBROMARONEChEMBLPhase 4 (approved)HRH1
BENZTROPINEChEMBLPhase 4 (approved)HRH1
BEPRIDILChEMBLPhase 4 (approved)HRH1
BETAMETHASONE PHOSPHORIC ACIDChEMBLPhase 4 (approved)HRH1
BIPERIDENChEMBLPhase 4 (approved)HRH1
BREXPIPRAZOLEChEMBLPhase 4 (approved)HRH1
BROMPERIDOLChEMBLPhase 4 (approved)HRH1
BROMPHENIRAMINEChEMBLPhase 4 (approved)HRH1
BUCLIZINEChEMBLPhase 4 (approved)HRH1
BUPROPIONChEMBLPhase 4 (approved)HRH1
BUSPIRONEChEMBLPhase 4 (approved)HRH1
BUTRIPTYLINEChEMBLPhase 4 (approved)HRH1
CABERGOLINEChEMBLPhase 4 (approved)HRH1
CANDESARTAN CILEXETILChEMBLPhase 4 (approved)HRH1
CAPTOPRILChEMBLPhase 4 (approved)HRH1
CARBINOXAMINEChEMBLPhase 4 (approved)HRH1
CARIPRAZINEChEMBLPhase 4 (approved)HRH1
CETIRIZINEChEMBLPhase 4 (approved)HRH1
CHLORDIAZEPOXIDEChEMBLPhase 4 (approved)HRH1
CHLORPHENIRAMINEChEMBLPhase 4 (approved)HRH1
CHLORPHENTERMINEChEMBLPhase 4 (approved)HRH1
CHLORPROMAZINEChEMBLPhase 4 (approved)HRH1
CHLORPROTHIXENEChEMBLPhase 4 (approved)HRH1
CINACALCETChEMBLPhase 4 (approved)HRH1
CINNARIZINEChEMBLPhase 4 (approved)HRH1
CISAPRIDEChEMBLPhase 4 (approved)HRH1
CITALOPRAMChEMBLPhase 4 (approved)HRH1
CLEMASTINEChEMBLPhase 4 (approved)HRH1
CLOFAZIMINEChEMBLPhase 4 (approved)HRH1
CLOMIPRAMINEChEMBLPhase 4 (approved)HRH1
CLOTRIMAZOLEChEMBLPhase 4 (approved)HRH1
CLOZAPINEChEMBLPhase 4 (approved)HRH1
CYCLIZINEChEMBLPhase 4 (approved)HRH1
CYCLOBENZAPRINEChEMBLPhase 4 (approved)HRH1
CYPROHEPTADINEChEMBLPhase 4 (approved)HRH1
DAUNORUBICINChEMBLPhase 4 (approved)HRH1
DESIPRAMINEChEMBLPhase 4 (approved)HRH1
DEXBROMPHENIRAMINEChEMBLPhase 4 (approved)HRH1