Timolol

Summary

Timolol (CHEMBL499) is an approved small-molecule antiglaucoma drug (ATC C07AA06) targeting ADRB1 and ADRB2; indicated across 15 conditions including open-angle glaucoma and cardiovascular disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: C07AA06 (+2 more)
• Targets: 2 (ADRB1, ADRB2)
• Indications: 15 conditions
• Clinical trials: 117
• Chemistry: 316.42 Da · C13H24N4O3S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL499
Name	Timolol
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	33624
ChEBI	CHEBI:9599
ATC	C07AA06, S01ED51, S01ED01
Molecular formula	C13H24N4O3S
Molecular weight	316.42
InChIKey	BLJRIMJGRPQVNF-JTQLQIEISA-N

SMILES: CC(C)(C)NC[C@@H](COC1=NSN=C1N2CCOCC2)O

IUPAC name: (2S)-1-(tert-butylamino)-3-[(4-morpholin-4-yl-1,2,5-thiadiazol-3-yl)oxy]propan-2-ol

ChEBI definition: The (S)-(−) (more active) enantiomer of timolol. A beta-adrenergic antagonist, both the hemihydrate and the maleate salt are used in the mangement of glaucoma, hypertension, angina pectoris and myocardial infarction, and for the prevention of migraine.

Pharmacological roles (ChEBI): antiglaucoma drug, antihypertensive agent, anti-arrhythmia drug, β-adrenergic antagonist.

Also known as: Betim, Betimol, Blocadren, Glau-opt, Glaucol, Nyogel, Timolol, Timolol anhydrous, Timolol hemihydrate, Tiopex, timolol, SID11111904

Parent form; salt/anhydrous children: CHEMBL1200870

Patent coverage: 11,355 distinct patent families (43,652 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
ADRB1	β1-adrenoceptor	Antagonist	9	0%	P08588
ADRB2	β2-adrenoceptor	Antagonist	9.7	0.4%	P07550

Broader ChEMBL bioactivity targets: 15 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, D(1A) dopamine receptor, Beta-2 adrenergic receptor, Beta-1 adrenergic receptor, 5-hydroxytryptamine receptor 1A, Beta-3 adrenergic receptor, 5-hydroxytryptamine receptor 1A, Muscarinic acetylcholine receptor M1, Sigma non-opioid intracellular receptor 1, Cytochrome P450 2D6.

Bioactivity

ChEMBL activities: 32 potent at pChembl ≥ 5 of 42 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
Q8K4Z4	9.78	Kd	0.17	nM	CHEMBL_ACT_1065560
ADRB2	9.7	Ki	0.2	nM	CHEMBL_ACT_7819345
ADRB2	9.68	Ki	0.21	nM	CHEMBL_ACT_18377936
ADRB2	9.67	IC50	0.22	nM	CHEMBL_ACT_25751281
Q8K4Z4	9.62	Kd	0.24	nM	CHEMBL_ACT_544740
Q8K4Z4	9.62	Kd	0.24	nM	CHEMBL_ACT_65714
ADRB2	9.54	IC50	0.29	nM	CHEMBL_ACT_7819344
ADRB1	8.82	Ki	1.5	nM	CHEMBL_ACT_7819343
ADRB2	8.73	Ki	1.86	nM	CHEMBL_ACT_25741109
ADRB2	8.7	AC50	2	nM	CHEMBL_ACT_25123278
ADRB1	8.59	AC50	2.6	nM	CHEMBL_ACT_25122269
ADRB1	8.59	IC50	2.6	nM	CHEMBL_ACT_7819342
P18090	8.5	Ki	3.16	nM	CHEMBL_ACT_1720556
ADRB1	8.27	Ki	5.37	nM	CHEMBL_ACT_18377915
ADRB1	8.22	Ki	6.02	nM	CHEMBL_ACT_25741108
P18090	8.1	Ki	7.94	nM	CHEMBL_ACT_1720560
P18090	7.8	Ki	15.85	nM	CHEMBL_ACT_1720557
P18090	7.5	Ki	31.62	nM	CHEMBL_ACT_1720561
ADRB3	6.47	Ki	339	nM	CHEMBL_ACT_7819347
SIGMAR1	6.41	Ki	391.2	nM	CHEMBL_ACT_25741111
ADRB3	6.34	IC50	452	nM	CHEMBL_ACT_7819346
P19327	6.21	Ki	616.6	nM	CHEMBL_ACT_836418
P18090	6.2	Ki	631	nM	CHEMBL_ACT_1720558
P19327	5.81	Ki	1550	nM	CHEMBL_ACT_7823533
P19327	5.57	IC50	2712	nM	CHEMBL_ACT_7823532
HTR1A	5.38	AC50	4200	nM	CHEMBL_ACT_25216370
P08482	5.3	Potency	5012	nM	CHEMBL_ACT_4799520
DRD1	5.28	Ki	5281	nM	CHEMBL_ACT_25741110
CYP2D6	5.1	Potency	7943	nM	CHEMBL_ACT_4994365
CYP2D6	5.1	AC50	7943	nM	CHEMBL_ACT_6050268

Target pathways

Aggregated over 2 target gene(s): ADRB1, ADRB2.

Top Reactome pathways

16 total, by targets touching each:

Pathway	Targets	Genes
Signal Transduction	2	ADRB1, ADRB2
Signaling by GPCR	2	ADRB1, ADRB2
Class A/1 (Rhodopsin-like receptors)	2	ADRB1, ADRB2
Amine ligand-binding receptors	2	ADRB1, ADRB2
GPCR downstream signalling	2	ADRB1, ADRB2
Adrenoceptors	2	ADRB1, ADRB2
G alpha (s) signalling events	2	ADRB1, ADRB2
GPCR ligand binding	2	ADRB1, ADRB2
Membrane Trafficking	1	ADRB2
Metabolism of proteins	1	ADRB2
Vesicle-mediated transport	1	ADRB2
Deubiquitination	1	ADRB2
Ub-specific processing proteases	1	ADRB2
Post-translational protein modification	1	ADRB2
Cargo recognition for clathrin-mediated endocytosis	1	ADRB2
Clathrin-mediated endocytosis	1	ADRB2

Dominant GO biological processes

GO term	Targets
diet induced thermogenesis	2
norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure	2
adenylate cyclase-activating G protein-coupled receptor signaling pathway	2
response to cold	2
positive regulation of cardiac muscle cell apoptotic process	2
heat generation	2
negative regulation of multicellular organism growth	2
positive regulation of MAPK cascade	2
brown fat cell differentiation	2
adenylate cyclase-activating adrenergic receptor signaling pathway	2
positive regulation of cold-induced thermogenesis	2
signal transduction	2
G protein-coupled receptor signaling pathway	2
positive regulation of heart rate by epinephrine-norepinephrine	1
positive regulation of the force of heart contraction by epinephrine-norepinephrine	1

Indications & clinical

Indications

15 indications (4 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
open-angle glaucoma	4	MONDO:0005338	EFO:0004190
cardiovascular disorder	4	MONDO:0004995	EFO:0000319
ocular hypertension	4	MONDO:0006875	EFO:1001069
glaucoma	4	MONDO:0005041	MONDO:0005041
melanoma	3	MONDO:0005105	EFO:0000756
exfoliation syndrome	3	MONDO:0008327	EFO:0004235
paronychia	3	MONDO:0005898	EFO:0007421
hemangioma	2	MONDO:0006500	EFO:1000635
wet macular degeneration	2	MONDO:0005417	EFO:0004683
injury	2	MONDO:0021178	EFO:0000546
migraine disorder	2	MONDO:0005277	MONDO:0005277
hereditary hemorrhagic telangiectasia	2	MONDO:0019180	MONDO:0019180
age-related macular degeneration	2	MONDO:0005150	EFO:0001365
Sturge-Weber syndrome	1	MONDO:0008501	MONDO:0008501

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

Clinical trials

Total trials: 117.

Phase distribution

Phase	Trials
PHASE3	32
PHASE4	30
PHASE2	23
Not specified	18
PHASE1	7
PHASE1/PHASE2	3
EARLY_PHASE1	3
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00273429	PHASE4	COMPLETED	Cosopt Versus Xalatan
NCT00273442	PHASE4	COMPLETED	Assessing Cosopt Switch Patients
NCT00273481	PHASE4	COMPLETED	Cosopt Versus Xalacom
NCT00330577	PHASE4	COMPLETED	24-Hour Intraocular Pressure (IOP) And Blood Pressure Control In Glaucoma And Ocular Hypertension Patients
NCT00397241	PHASE4	COMPLETED	24-hour Study of Dorzolamide/Timolol and Latanoprost/Timolol Fixed Combinations
NCT00508469	PHASE4	COMPLETED	Adherence Assessment With Travalert Dosing Aid
NCT00735449	PHASE4	COMPLETED	Comparing Efficacy and Safety of Combigan With Timolol Adjunctive to Xalatan in Glaucoma or Ocular Hypertension Subjects
NCT00763061	PHASE4	COMPLETED	Travatan Versus Timoptic in Treating Open-angle Glaucoma or Ocular Hypertension
NCT00804648	PHASE4	COMPLETED	Patient Satisfaction With Timolol in Subjects With Open-Angle Glaucoma or Ocular Hypertension
NCT00913029	PHASE4	COMPLETED	Evaluation of the iStent Versus Two Ocular Hypotensive Agents in Patients With Primary Open-angle Glaucoma (POAG)
NCT00972257	PHASE4	COMPLETED	24-hr Intraocular Pressure Control With Dorzolamide/Timolol vs the Brimonidine/Timolol Fixed Combination
NCT01111890	PHASE4	COMPLETED	Comparison of the Efficacy of AZARGA® Versus COSOPT® in Patients With Open-Angled Glaucoma or Ocular Hypertension
NCT01250457	PHASE4	WITHDRAWN	Topical Timolol for the Treatment of Benign Vascular Periocular Lesions
NCT01446497	PHASE4	UNKNOWN	Efficacy and Safety Study of Combigan and 0.5% Timoptic in Normal Tension Glaucoma
NCT01655758	PHASE4	COMPLETED	24-hour Control of Intraocular Pressure (IOP) in Ocular Hypertension
NCT01881126	PHASE4	COMPLETED	An Efficacy and Safety Study of Bimatoprost 0.01% Alone Compared With Travoprost 0.004% and Timolol 0.5% in Subjects With Glaucoma or Ocular Hypertension
NCT01927406	PHASE4	WITHDRAWN	The Secondary Beneficial Effects of Prostaglandin Analog Treatment in Thyroid Eye Disease Patients.
NCT01978600	PHASE4	COMPLETED	Evaluation of Intraocular Pressure Using Simbrinza™ in Patients With Open-Angle Glaucoma or Ocular Hypertension
NCT02053298	PHASE4	COMPLETED	Impact of Timolol/Dorzolamide Therapy on Autoregulation in Glaucoma Patients
NCT02097719	PHASE4	COMPLETED	Efficacy and Safety Study of Bimatoprost 0.01% Alone Compared With Travoprost 0.004% and Timolol 0.5% in Subjects With Glaucoma or Ocular Hypertension
NCT02802137	PHASE4	COMPLETED	24-hour Efficacy and Ocular Surface With Talfuprost and Triple Combined Therapy
NCT03323164	PHASE4	COMPLETED	Peripapillary Blood Flow After Use of Anti-glaucoma Medications: An OCT Angiography Study
NCT03966560	PHASE4	COMPLETED	Choroidal Thickness and Its Correlations With Ocular Parameters in Primary Open-angle Glaucoma
NCT04098861	PHASE4	UNKNOWN	Efficacy and Safety of Latanoprost/Timolol for Primary Open Angle Glaucoma
NCT04288700	PHASE4	UNKNOWN	Evaluation of the Efficacy of Captopril Versus Propranolol and Timolol as a Treatment of Infantile Capillary Hemangioma
NCT04412096	PHASE4	COMPLETED	Aqueous Humor Dynamic Components That Determine Intraocular Pressure Variance
NCT05299593	PHASE4	UNKNOWN	24-hour Efficacy and Tolerability of the Tafluprost-timolol Fixed Association Without Preservatives in Glaucomatous or Ocular Hypertensive Patients Already Treated With Latanoprost Preserved With BAK. A Prospective, Open Study of 3 Months Duration.
NCT05479123	PHASE4	TERMINATED	Assessing the Impact of Dosage Frequency of Propranolol on Sleep Patterns in Patients With Infantile Hemangiomas
NCT05857267	PHASE4	COMPLETED	Dorzolamide+Timolol Multidose Preservative-free vs Dorzolamida+Timolol BAK Preserved Efficacy and Safety
NCT06369077	PHASE4	TERMINATED	How Much Does Reduced Dosing of Latanoprost and Dorzolamide-timolol Affect Pressure?
NCT06643416	PHASE3	RECRUITING	Efficacy and Safety of Add-on Timolol for EGFR-TKI and ALK-TKI Induced Paronychia
NCT00006398	PHASE3	COMPLETED	Prevention of Esophageal Varices by Beta-Adrenergic Blockers
NCT00159653	PHASE3	COMPLETED	A 12-Week, Randomized, Double-Masked, Parallel Group Comparison Of Evening Dosing With Xalacom In Subjects With Glaucoma
NCT00219596	PHASE3	COMPLETED	Xalacom And Combination Of Unfixed Latanoprost And Timolol In Subjects With Open-Angle Glaucoma Or Ocular Hypertension
NCT00277498	PHASE3	COMPLETED	A 12-week, Randomized, Double-masked, Parallel Group Comparison of Evening Dosing With Xalacom in Subjects With Glaucoma
NCT00293787	PHASE3	COMPLETED	A Study of Glaucoma Therapy to Treat Open-Angle Glaucoma or Ocular Hypertension
NCT00293800	PHASE3	COMPLETED	A Study of Glaucoma Therapy to Treat Open-Angle Glaucoma or Ocular Hypertension
NCT00314158	PHASE3	COMPLETED	A Study of a Glaucoma Therapy to Treat Open-Angle Glaucoma or Ocular Hypertension
NCT00333125	PHASE3	COMPLETED	A Study of Glaucoma Therapy to Treat Open-Angle Glaucoma or Ocular Hypertension
NCT00652106	PHASE3	COMPLETED	Safety and Efficacy Study of Brimonidine/Timolol Fixed Combination in Patients With Glaucoma or Ocular Hypertension

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 3 clinical and 6 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.

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

Molecule	Source	Status	Shared targets
Desloratadine	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2
Dihydroergotamine	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2
OLODATEROL	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2
Pramipexole	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2
TAMSULOSIN	ChEMBL + PubChem	Phase 4 (approved)	ADRB1, ADRB2
ACEBUTOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ALBUTEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
AMITRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ARFORMOTEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ATENOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
BENPERIDOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
BETAXOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
BISOPROLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
BREXPIPRAZOLE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
BROMOCRIPTINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CARTEOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CARVEDILOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CELIPROLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CLEMASTINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CLOMIPRAMINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
CLOTRIMAZOLE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
DARIFENACIN	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
DOBUTAMINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
DOMPERIDONE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
EPINEPHRINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ERGOTAMINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ESMOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
FENOTEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
FLUSPIRILENE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
FORMOTEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
INDACATEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
LABETALOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
LEVOBUNOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
METOPROLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
MONTELUKAST	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
NADOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
NEBIVOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
NITAZOXANIDE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
NOREPINEPHRINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
NORTRIPTYLINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
OXPRENOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PHENYLEPHRINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PIMOZIDE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PINDOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PRACTOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PRENYLAMINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PRIMAQUINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PROPAFENONE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
PROPRANOLOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
RANOLAZINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
RIFAMPIN	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
RIFAXIMIN	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
RITODRINE	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
SALMETEROL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
SOTALOL	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2
SUNITINIB	ChEMBL	Phase 4 (approved)	ADRB1, ADRB2