Apraclonidine
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Also known as ApraclonidinaIopidineSID11110712SID90341674SID50110931
Summary
Apraclonidine (CHEMBL647) is an approved small-molecule α-adrenergic agonist (ATC S01EA03) targeting ADRA2A and ADRA2C; indicated across 2 conditions including glaucoma and myasthenia gravis.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: S01EA03
- Targets: 2 (ADRA2A, ADRA2C)
- Indications: 2 conditions
- Clinical trials: 4
- Chemistry: 245.11 Da · C9H10Cl2N4
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL647 |
| Name | Apraclonidine |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 2216 |
| ChEBI | CHEBI:2788 |
| ATC | S01EA03 |
| Molecular formula | C9H10Cl2N4 |
| Molecular weight | 245.11 |
| InChIKey | IEJXVRYNEISIKR-UHFFFAOYSA-N |
SMILES: C1CN=C(N1)NC2=C(C=C(C=C2Cl)N)Cl
IUPAC name: 2,6-dichloro-1-N-(4,5-dihydro-1H-imidazol-2-yl)benzene-1,4-diamine
ChEBI definition: An imidazoline that is 2-amino 4,5-dihydro-1H-imidazoline in which one of the exocyclic amino hydrogens has been replaced by a 4-amino-2,6-dichlorophenyl group.
Pharmacological roles (ChEBI): α-adrenergic agonist, antiglaucoma drug, ophthalmology drug, β-adrenergic agonist, diagnostic agent.
Also known as: Apraclonidina, Apraclonidine, Iopidine, SID11110712, SID90341674, SID50110931, apraclonidine, APRACLONIDINE
Parent form; salt/anhydrous children: CHEMBL1200379
Patent coverage: 3,562 distinct patent families (13,743 SureChEMBL compound mentions), from 2 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 |
|---|---|---|---|---|---|
| ADRA2A | α2A-adrenoceptor | Agonist | 8.5 | 0.1% | P08913 |
| ADRA2C | α2C-adrenoceptor | Agonist | 7.52 | 0% | P18825 |
Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Thyrotropin receptor, Adrenergic receptor alpha-1, Adrenergic receptor alpha-2, Alpha-2B adrenergic receptor, Muscarinic acetylcholine receptor M1, Nuclear factor NF-kappa-B p105 subunit, 3-hydroxyacyl-CoA dehydrogenase type-2.
Bioactivity
ChEMBL activities: 8 potent at pChembl ≥ 5 of 12 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| ADRA2A | 8.72 | EC50 | 1.9 | nM | CHEMBL_ACT_70029 |
| ADRA2A | 8.54 | Ki | 2.9 | nM | CHEMBL_ACT_70025 |
| ADRA2A | 8.4 | IC50 | 4 | nM | CHEMBL_ACT_227881 |
| P19328 | 8.32 | Ki | 4.8 | nM | CHEMBL_ACT_70026 |
| ADRA2C | 7.52 | Ki | 30 | nM | CHEMBL_ACT_70027 |
| ADRA1D | 6.75 | Ki | 180 | nM | CHEMBL_ACT_70024 |
| ADRA1D | 6.75 | EC50 | 180 | nM | CHEMBL_ACT_70028 |
| HSD17B10 | 5.9 | Potency | 1259 | nM | CHEMBL_ACT_4849616 |
Target pathways
Aggregated over 2 target gene(s): ADRA2A, ADRA2C.
Top Reactome pathways
19 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Hemostasis | 2 | ADRA2A, ADRA2C |
| Metabolism | 2 | ADRA2A, ADRA2C |
| Signal Transduction | 2 | ADRA2A, ADRA2C |
| Integration of energy metabolism | 2 | ADRA2A, ADRA2C |
| Signaling by GPCR | 2 | ADRA2A, ADRA2C |
| Class A/1 (Rhodopsin-like receptors) | 2 | ADRA2A, ADRA2C |
| Amine ligand-binding receptors | 2 | ADRA2A, ADRA2C |
| GPCR downstream signalling | 2 | ADRA2A, ADRA2C |
| Adrenoceptors | 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 |
| GPCR ligand binding | 2 | ADRA2A, ADRA2C |
| Surfactant metabolism | 2 | ADRA2A, ADRA2C |
| Platelet activation, signaling and aggregation | 2 | ADRA2A, ADRA2C |
| Platelet Aggregation (Plug Formation) | 2 | ADRA2A, ADRA2C |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| epidermal growth factor receptor signaling pathway | 2 |
| G protein-coupled receptor signaling pathway | 2 |
| negative regulation of norepinephrine secretion | 2 |
| regulation of vasoconstriction | 2 |
| platelet activation | 2 |
| negative regulation of epinephrine secretion | 2 |
| positive regulation of MAPK cascade | 2 |
| negative regulation of insulin secretion | 2 |
| positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 2 |
| adrenergic receptor signaling pathway | 2 |
| adenylate cyclase-inhibiting adrenergic receptor signaling pathway | 2 |
| regulation of smooth muscle contraction | 2 |
| signal transduction | 2 |
| positive regulation of cytokine production | 1 |
| DNA replication | 1 |
Indications & clinical
Indications
2 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 |
|---|---|---|---|
| glaucoma | 4 | MONDO:0005041 | MONDO:0005041 |
| myasthenia gravis | 2 | MONDO:0009688 | EFO:0004991 |
Clinical trials
Total trials: 4.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 1 |
| PHASE3 | 1 |
| PHASE2 | 1 |
| Not specified | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT05167760 | PHASE4 | WITHDRAWN | Efficacy of Topical Apraclonidine for the Treatment of Ocular Synkinesis |
| NCT06444529 | PHASE3 | COMPLETED | A Double-Masked Comparison of FID 123320 Ophthalmic Solution to Vehicle for the Reduction of Ocular Redness |
| NCT05045248 | PHASE2 | COMPLETED | Efficacy of Apraclonidine Eye Drops in the Treatment of Ptosis Secondary to Myasthenia Gravis |
| NCT00567411 | Not specified | UNKNOWN | Comparison of the Alpha-2 Agonists for Prevention of Intraocular Pressure Elevation After Selective Laser Trabeculoplasty |
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.
565 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| ACLIDINIUM BROMIDE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| CHENODIOL | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| CLOZAPINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| CRIZOTINIB | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| DESLORATADINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| DIHYDROERGOTAMINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| GENTIAN VIOLET | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| NAPHAZOLINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| OLANZAPINE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| OLODATEROL | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| PALIPERIDONE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| PRAMIPEXOLE | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| TAMSULOSIN | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| TEGASEROD | ChEMBL + PubChem | Phase 4 (approved) | ADRA2A, ADRA2C |
| ACETOPHENAZINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| ALFUZOSIN | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| AMISULPRIDE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| AMITRIPTYLINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| AMLODIPINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| ANTAZOLINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| APOMORPHINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| ASENAPINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| ATRACURIUM | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| AZELASTINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BAZEDOXIFENE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BENPERIDOL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BENZQUINAMIDE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BENZTHIAZIDE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BITHIONOL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BOSUTINIB | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BREXPIPRAZOLE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BRIMONIDINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BROMOCRIPTINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| BUFLOMEDIL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CABERGOLINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CABOZANTINIB | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CARIPRAZINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CHLORHEXIDINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CHLOROQUINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CISAPRIDE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CLONIDINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| CYPROHEPTADINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| DANAZOL | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| DARIFENACIN | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| DEXMEDETOMIDINE | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
| DEXTROMETHORPHAN | ChEMBL | Phase 4 (approved) | ADRA2A, ADRA2C |
Related Atlas pages
- Genes: ADRA2A, ADRA2C
- Diseases: glaucoma
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