Identification
- Summary
Brinzolamide is a carbonic anhydrase inhibitor used for the reduction of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.
- Brand Names
- Azarga, Azopt, Simbrinza
- Generic Name
- Brinzolamide
- DrugBank Accession Number
- DB01194
- Background
Brinzolamide is a highly specific, non-competitive, reversible carbonic anhydrase II (CA-II) inhibitor indicated to reduce ocular pressure in patients with ocular hypertension or open-angle glaucoma.5 Although the exact pathophysiology of glaucoma is still unknown, one of the main hallmarks of this disease is vascular dysregulation and abnormalities.1,2 The resulting vascular resistance increases intraocular pressure, thus impairing ocular perfusion.1,2 Although systemic anti-carbonic anhydrase (CA) therapy has been used for almost 50 years with varying degrees of success, systemic administration results in an increase in incidences of adverse effects.1,2
Brinzolamide was developed as a topical solution to the systemic side effects and dorzolamide, the first-ever approved topical CA inhibitor with contrasting results and evidence.2 Unlike dorzolamide, brinzolamide has a higher lipophilicity to facilitate diffusion across the blood-retinal barrier.2 Brinzolamide was approved by the FDA in 1998 as a standalone product and in 2013 as a combination product with brimonidine tartrate.5,6 In Europe, it was also approved as a combination product with timolol in 2008.7
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Brinzolamide (DB01194)
- Weight
- Average: 383.507
Monoisotopic: 383.064332867 - Chemical Formula
- C12H21N3O5S3
- Synonyms
- Brinzolamida
- Brinzolamide
- External IDs
- AL-4862
Pharmacology
- Indication
Brinzolamide, either as a standalone agent or in combination with brimonidine, is approved by the FDA for the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.8,5 Brinzolamide is also approved in Europe to be used in combination with timolol to treat the same conditions.7
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to manage Elevated intraocular pressure Combination Product in combination with: Timolol (DB00373) •••••••••••• •••••••••• •••••••• •• ••••••••••• ••••••••••• •••••••••• • ••••• Used in combination to manage Elevated intraocular pressure Combination Product in combination with: Timolol (DB00373) •••••••••••• •••••••••• •••••••• •• ••••••••••• ••••••••••• •••••••••• • ••••• Treatment of Increased intra ocular pressure (iop) •••••••••••• ••••••••••• •••••••••• • ••••• Used in combination to treat Increased intra ocular pressure (iop) Combination Product in combination with: Brimonidine (DB00484) •••••••••••• ••••••••••• •••••••••• • ••••• Treatment of Increased intra ocular pressure (iop) •••••••••••• ••••••••••• •••••••••• • ••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Inhibition of carbonic anhydrase II (CA-II) in the ciliary process of the eye slows the formation of bicarbonate and thus fluid flow, lowering intraocular pressure (IOP).3,4
The IOP-reducing effect of brinzolamide as adjunctive therapy to the prostaglandin analog travoprost was studied. Following a 4-week run-in with travoprost, patients with an IOP ≥19 mmHg were randomized to receive added treatment with brinzolamide or timolol. An additional decrease in mean diurnal IOP of 3.2 to 3.4 mmHg for the brinzolamide group and 3.2 to 4.2 mmHg for the timolol group were observed. There was an overall higher incidence of non-serious ocular adverse reactions, mainly related to signs of local irritation, in the brinzolamide/travoprost groups. The events were mild and did not affect the overall discontinuation rates in the studies.11
A clinical trial was conducted with brinzolamide in 32 pediatric patients less than 6 years of age, diagnosed with glaucoma or ocular hypertension. Some patients were naive to IOP therapy whilst others were on other IOP-lowering medicinal product(s). Those who had been on previous IOP medicinal products were not required to discontinue their IOP medicinal product(s) until the initiation of monotherapy with brinzolamide.11
Among patients who were naive to IOP therapy (10 patients), the efficacy of brinzolamide was similar to that seen previously in adults, with mean IOP reductions from baseline ranging up to 5 mmHg. Among patients who were on topical IOP-lowering medicinal products (22 patients), mean IOP increased slightly from baseline in the brinzolamide group.11
- Mechanism of action
Brinzolamide is a highly specific, reversible, non-competitive inhibitor of carbonic anhydrases (CA), the enzymes catalyzing the reversible reaction of water and carbon dioxide (CO2) to form bicarbonate ions.3 Although there are 7 isoforms of CA in human tissues, brinzolamide has the highest affinity to CA II.3,4 Brinzolamide and its active metabolites were not found to displace any known ligands in vitro from their respective receptors or enzymes commonly involved in producing side effects or ancillary pharmacology, thus explaining brinzolamide's high order of safety.4
Target Actions Organism ACarbonic anhydrase 2 inhibitorHumans UCarbonic anhydrase 1 inhibitorHumans UCarbonic anhydrase 4 inhibitorHumans UCarbonic anhydrase 5A, mitochondrial inhibitorHumans UCarbonic anhydrase 3 inhibitorHumans - Absorption
Brinzolamide is absorbed through the cornea following topical ocular administration. The substance is also absorbed into the systemic circulation where it binds strongly to carbonic anhydrase in red blood cells (RBCs). Plasma concentrations are very low.10
- Volume of distribution
Not Available
- Protein binding
Binding to plasma proteins is approximately 60%.8
- Metabolism
Brinzolamide is metabolized by hepatic cytochrome P450 isozymes, specifically CYP3A4, CYP2A6, CYP2B6, CYP2C8 and CYP2C9. The primary metabolite is N-desethylbrinzolamide followed by the N-desmethoxypropyl and O-desmethyl metabolites as well as an N-propionic acid analog formed by oxidation of the N-propyl side chain of O-desmethyl brinzolamide. Brinzolamide and N-desethylbrinzolamide do not inhibit cytochrome P450 isozymes at concentrations at least 100-fold above maximum systemic levels.10
Brimonidine is extensively metabolized by hepatic aldehyde oxidase with the formation of 2-oxobrimonidine, 3-oxobrimonidine, and 2,3-dioxobrimonidine being the major metabolites. Oxidative cleavage of the imidazoline ring to 5-bromo-6-guanidinoquinoxaline is also observed.10
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- Route of elimination
Brinzolamide is eliminated predominantly in the urine as unchanged drug.8N-Desethyl brinzolamide is also found in the urine along with lower concentrations of the N-desmethoxypropyl and O-desmethyl metabolites.8
- Half-life
Due to its affinity for CAII, brinzolamide distributes extensively into the red blood cells (RBCs) and exhibits a long half-life in whole blood (approximately 111 days).8
- Clearance
Not Available
- Adverse Effects
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Developmental toxicity studies with brinzolamide in rabbits at oral doses of 1, 3, and 6 mg/kg/day (20, 60, and 120 times the recommended human ophthalmic dose) produced maternal toxicity at 6 mg/kg/day and a significant increase in the number of fetal variations, such as accessory skull bones, which was only slightly higher than the historical value at 1 and 6 mg/kg. In rats, statistically, decreased body weights of fetuses from dams receiving oral doses of 18 mg/kg/day (180 times the recommended human ophthalmic dose) during gestation were proportional to the reduced maternal weight gain, with no statistically significant effects on organ or tissue development. Increases in unossified sternebrae, reduced ossification of the skull, and unossified hyoid that occurred at 6 and 18 mg/kg were not statistically significant. No treatment-related malformations were seen. Following oral administration of 14C-brinzolamide 14Cbrinzolamide to pregnant rats, radioactivity was found to cross the placenta and was present in the fetal tissues and blood.8
Developmental toxicity studies performed in rats with oral doses of 0.66 mg brimonidine base/kg revealed no evidence of harm to the fetus. Dosing at this level resulted in a plasma drug concentration approximately 100 times higher than that seen in humans at the recommended human ophthalmic dose. In animal studies, brimonidine crossed the placenta and entered into fetal circulation to a limited extent.8
There are no adequate and well-controlled studies in pregnant women. Brinzolamide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.8
Brinzolamide caused urinary bladder tumors in female mice at oral doses of 10 mg/kg/day and in male rats at oral doses of 8 mg/kg/day in 2-year studies. Brinzolamide was not carcinogenic in male mice or female rats dosed orally for up to 2 years. The carcinogenicity appears secondary to kidney and urinary bladder toxicity. These levels of exposure cannot be achieved with topical ophthalmic dosing in humans.8
The following tests for the mutagenic potential of brinzolamide were negative: (1) in vivo mouse micronucleus assay; (2) in vivo sister chromatid exchange assay; and (3) Ames E. coli test. The in vitro mouse lymphoma forward mutation assay was negative in the absence of activation, but positive in the presence of microsomal activation. In this assay, there was no consistent dose-response relationship to the increased mutation frequency and cytotoxicity likely contributed to the high mutation frequency. Carbonic anhydrase inhibitors, as a class, are not mutagenic and the weight of evidence supports that brinzolamide is consistent with the class. In reproduction studies of brinzolamide in rats, there were no adverse effects on the fertility or reproductive capacity of males or females at doses up to 18 mg/kg/day (180 times the recommended human ophthalmic dose).8
Brimonidine tartrate was not carcinogenic in either a 21-month mouse or 24-month rat study. In these studies, dietary administration of brimonidine tartrate at doses up to 2.5 mg/kg/day in mice and 1 mg/kg/day in rats resulted in plasma drug concentrations 80 and 120 times higher than the human plasma drug level at the recommended clinical dose, respectively. Brimonidine tartrate was not mutagenic or cytogenic in a series of in vitro and in vivo studies including the Ames test, chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells, a host-mediated assay and cytogenic studies in mice, and a dominant lethal assay. In reproductive studies performed in rats with oral doses of 0.66 mg brimonidine base/kg (approximately 100 times the plasma drug concentration level seen in humans following multiple ophthalmic doses), fertility was not impaired.8
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Brinzolamide can be increased when it is combined with Abametapir. Acetazolamide The risk or severity of adverse effects can be increased when Brinzolamide is combined with Acetazolamide. Acetylsalicylic acid The risk or severity of electrolyte abnormality can be increased when Brinzolamide is combined with Acetylsalicylic acid. Aminosalicylic acid The risk or severity of electrolyte abnormality can be increased when Brinzolamide is combined with Aminosalicylic acid. Apalutamide The serum concentration of Brinzolamide can be decreased when it is combined with Apalutamide. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Azopt Suspension / drops 10 mg/ml Ophthalmic Novartis Europharm Limited 2020-12-17 Not applicable EU 
Azopt Suspension 1 % w/v Ophthalmic Novartis 1998-11-11 Not applicable Canada 
Azopt Suspension / drops 10 mg/ml Ophthalmic Novartis Europharm Limited 2020-12-17 Not applicable EU Azopt Suspension / drops 10 mg/1mL Ophthalmic ALCON LABORATORIES, INC. 1998-04-30 Not applicable US 
Azopt Suspension / drops 10 mg/1mL Ophthalmic Novartis Pharmaceuticals Corporation 1998-04-30 Not applicable US - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Brinzolamide Suspension / drops 10 mg/1mL Ophthalmic bryant ranch prepack 2023-10-10 Not applicable US Brinzolamide Suspension / drops 10 mg/1mL Ophthalmic Sandoz Inc 2021-03-08 Not applicable US Brinzolamide Suspension / drops 10 mg/1mL Ophthalmic Padagis US LLC 2023-10-10 Not applicable US Brinzolamide Suspension / drops 10 mg/1mL Ophthalmic bryant ranch prepack 2021-03-08 Not applicable US Brinzolamide Suspension / drops 10 mg/1mL Ophthalmic Actavis Pharma, Inc. 2021-03-08 Not applicable US - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image AZARGA Brinzolamide (10 mg/mL) + Timolol maleate (5 mg/mL) Solution / drops; Suspension / drops Ophthalmic 2017-01-01 Not applicable Germany 
Azarga Brinzolamide (10 mg/ml) + Timolol maleate (5 mg/ml) Suspension / drops Ophthalmic Novartis Europharm Limited 2016-09-20 Not applicable EU AZARGA Brinzolamide (10 mg/mL) + Timolol maleate (5 mg/mL) Solution / drops; Suspension / drops Ophthalmic 2017-01-01 Not applicable Germany AZARGA Brinzolamide (10 mg/mL) + Timolol maleate (5 mg/mL) Solution / drops; Suspension / drops Ophthalmic 2017-01-01 Not applicable Germany AZARGA Brinzolamide (10 mg/mL) + Timolol maleate (5 mg/mL) Solution / drops; Suspension / drops Ophthalmic 2017-01-01 Not applicable Germany
Categories
- ATC Codes
- S01EC54 — Brinzolamide, combinations
- S01EC — Carbonic anhydrase inhibitors
- S01E — ANTIGLAUCOMA PREPARATIONS AND MIOTICS
- S01 — OPHTHALMOLOGICALS
- S — SENSORY ORGANS
- S01EC — Carbonic anhydrase inhibitors
- S01E — ANTIGLAUCOMA PREPARATIONS AND MIOTICS
- S01 — OPHTHALMOLOGICALS
- S — SENSORY ORGANS
- Drug Categories
- Amides
- Antiglaucoma Preparations and Miotics
- Carbonic Anhydrase Inhibitors
- Cytochrome P-450 CYP2A6 Substrates
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 Substrates
- Diuretics
- Enzyme Inhibitors
- Genito Urinary System and Sex Hormones
- Gynecological Antiinfectives and Antiseptics
- Ophthalmics
- Ophthalmologicals
- Sensory Organs
- Sulfonamides
- Sulfones
- Sulfur Compounds
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as thienothiazines. These are heterocyclic compounds containing a thiophene ring fused to a thiazine. Thiophene is 5-membered ring consisting of four carbon atoms and one sulfur atom. Thiazine is a 6-membered ring consisting of four carbon, one nitrogen and one sulfur atoms.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Thienothiazines
- Sub Class
- Not Available
- Direct Parent
- Thienothiazines
- Alternative Parents
- 2,3,5-trisubstituted thiophenes / Aralkylamines / Organosulfonamides / 1,2-thiazines / Heteroaromatic compounds / Aminosulfonyl compounds / Dialkylamines / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds show 2 more
- Substituents
- 2,3,5-trisubstituted thiophene / Amine / Aminosulfonyl compound / Aralkylamine / Aromatic heteropolycyclic compound / Azacycle / Dialkyl ether / Ether / Heteroaromatic compound / Hydrocarbon derivative show 16 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- sulfonamide, thienothiazine (CHEBI:41212)
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 9451Z89515
- CAS number
- 138890-62-7
- InChI Key
- HCRKCZRJWPKOAR-JTQLQIEISA-N
- InChI
- InChI=1S/C12H21N3O5S3/c1-3-14-10-8-15(5-4-6-20-2)23(18,19)12-9(10)7-11(21-12)22(13,16)17/h7,10,14H,3-6,8H2,1-2H3,(H2,13,16,17)/t10-/m0/s1
- IUPAC Name
- (4R)-4-(ethylamino)-2-(3-methoxypropyl)-1,1-dioxo-2H,3H,4H-1lambda6-thieno[3,2-e][1,2]thiazine-6-sulfonamide
- SMILES
- CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S2)S(N)(=O)=O
References
- Synthesis Reference
Alessandro Falchi, Ottorino De Lucchi, Andrea Castellin, "PROCESS FOR THE PREPARATION OF BRINZOLAMIDE." U.S. Patent US20110118461, issued May 19, 2011.
US20110118461- General References
- Iester M, Altieri M, Michelson G, Vittone P, Traverso CE, Calabria G: Retinal peripapillary blood flow before and after topical brinzolamide. Ophthalmologica. 2004 Nov-Dec;218(6):390-6. [Article]
- Kaup M, Plange N, Niegel M, Remky A, Arend O: Effects of brinzolamide on ocular haemodynamics in healthy volunteers. Br J Ophthalmol. 2004 Feb;88(2):257-62. [Article]
- Iester M: Brinzolamide ophthalmic suspension: a review of its pharmacology and use in the treatment of open angle glaucoma and ocular hypertension. Clin Ophthalmol. 2008 Sep;2(3):517-23. [Article]
- DeSantis L: Preclinical overview of brinzolamide. Surv Ophthalmol. 2000 Jan;44 Suppl 2:S119-29. [Article]
- FDA Approved Drug Products: AZOPT (brinzolamide) suspension [Link]
- FDA Approved Drug Products: SIMBRINZA (brinzolamide and brimonidine tartrate) suspension [Link]
- EMA Product Information: AZARGA (brinzolamide and timolol maleate) suspension [Link]
- FDA Approved Drug Products: SIMBRINZA (brinzolamide and brimonidine tartrate ophthalmic suspension) 1%/0.2%, for topical ophthalmic use (May 2023) [Link]
- Brinzolamide MSDS [Link]
- EMA Approved Drug Products: SIMBRINZA (brinzolamide and brimonidine tartrate ophthalmic suspension) 1%/0.2@ for topical opththalmic use (May 2023) [Link]
- EMA Approved Drug Products: AZOPT (brinzolamide) suspension [Link]
- External Links
- Human Metabolome Database
- HMDB0015325
- KEGG Drug
- D00652
- KEGG Compound
- C07760
- PubChem Compound
- 68844
- PubChem Substance
- 46507071
- ChemSpider
- 62077
- BindingDB
- 10885
- 194881
- ChEBI
- 3176
- ChEMBL
- CHEMBL220491
- ZINC
- ZINC000003953037
- Therapeutic Targets Database
- DAP000602
- PharmGKB
- PA164744929
- PDBe Ligand
- BZ1
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Brinzolamide
- PDB Entries
- 3znc / 4m2r / 4m2v / 6bbs
- FDA label
- Download (580 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 4 Completed Not Available Ocular Hypertension / Open Angle Glaucoma (OAG) 1 4 Completed Prevention Ocular Hypertension / Posterior Capsule Opacification 1 4 Completed Treatment Glaucoma 11 4 Completed Treatment Glaucoma / Ocular Hypertension 6 4 Completed Treatment Glaucoma / Ocular Hypertension / Open Angle Glaucoma (OAG) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Alcon Laboratories
- Dosage Forms
Form Route Strength Solution / drops Ophthalmic Solution / drops; suspension / drops Ophthalmic Suspension Ophthalmic 10 mg/mL Solution / drops Ophthalmic Suspension Ophthalmic 1 % w/v Suspension / drops Ophthalmic 10 mg/1mL Solution / drops; suspension / drops Ophthalmic 10 MG/ML Suspension Ophthalmic Suspension Ophthalmic 10 MG/ML Solution Ophthalmic 10 mg/ml Suspension Conjunctival; Ophthalmic 10 mg Suspension Ophthalmic 10.000 mg Solution / drops Ophthalmic 10 MG/ML Suspension / drops Ophthalmic 10 mg/ml Powder Not applicable 25 kg/1 Solution / drops Ophthalmic 1 % Suspension Ophthalmic 1 % Suspension Ophthalmic Suspension / drops Ophthalmic - Prices
Unit description Cost Unit Azopt 1% Suspension 15ml Bottle 163.11USD bottle Azopt 1% Suspension 10ml Bottle 108.83USD bottle Azopt 1% eye drops 8.05USD ml Azopt 1 % Suspension 3.63USD ml DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US5461081 No 1995-10-24 2013-04-24 US US5240923 No 1993-08-31 2010-08-31 US CA2080223 No 2000-11-07 2011-04-03 Canada US6316441 No 2001-11-13 2019-12-07 US US9044484 No 2015-06-02 2030-10-30 US US9421265 No 2016-08-23 2030-06-17 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 131 - 132 °C L46382 - Predicted Properties
Property Value Source Water Solubility 0.713 mg/mL ALOGPS logP -0.65 ALOGPS logP -0.58 Chemaxon logS -2.7 ALOGPS pKa (Strongest Acidic) 8.18 Chemaxon pKa (Strongest Basic) 6.5 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 118.8 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 87.2 m3·mol-1 Chemaxon Polarizability 37.93 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9765 Blood Brain Barrier + 0.8754 Caco-2 permeable - 0.7123 P-glycoprotein substrate Substrate 0.8185 P-glycoprotein inhibitor I Non-inhibitor 0.6795 P-glycoprotein inhibitor II Non-inhibitor 0.9245 Renal organic cation transporter Non-inhibitor 0.8276 CYP450 2C9 substrate Non-substrate 0.7897 CYP450 2D6 substrate Non-substrate 0.9116 CYP450 3A4 substrate Substrate 0.6431 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Non-inhibitor 0.907 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.8309 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8588 Ames test Non AMES toxic 0.5982 Carcinogenicity Non-carcinogens 0.7712 Biodegradation Not ready biodegradable 0.9834 Rat acute toxicity 2.4930 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7097 hERG inhibition (predictor II) Non-inhibitor 0.5167
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 193.500788 predictedDarkChem Lite v0.1.0 [M-H]- 191.693288 predictedDarkChem Lite v0.1.0 [M-H]- 181.31767 predictedDeepCCS 1.0 (2019) [M+H]+ 194.317388 predictedDarkChem Lite v0.1.0 [M+H]+ 192.511888 predictedDarkChem Lite v0.1.0 [M+H]+ 183.67567 predictedDeepCCS 1.0 (2019) [M+Na]+ 193.399588 predictedDarkChem Lite v0.1.0 [M+Na]+ 192.395188 predictedDarkChem Lite v0.1.0 [M+Na]+ 190.96211 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion in...
- Gene Name
- CA2
- Uniprot ID
- P00918
- Uniprot Name
- Carbonic anhydrase 2
- Molecular Weight
- 29245.895 Da
References
- Stams T, Chen Y, Boriack-Sjodin PA, Hurt JD, Liao J, May JA, Dean T, Laipis P, Silverman DN, Christianson DW: Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme-drug discrimination. Protein Sci. 1998 Mar;7(3):556-63. [Article]
- DeSantis L: Preclinical overview of brinzolamide. Surv Ophthalmol. 2000 Jan;44 Suppl 2:S119-29. [Article]
- Winum JY, Casini A, Mincione F, Starnotti M, Montero JL, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines as topically acting antiglaucoma agents in hypertensive rabbits. Bioorg Med Chem Lett. 2004 Jan 5;14(1):225-9. [Article]
- Boriack-Sjodin PA, Zeitlin S, Chen HH, Crenshaw L, Gross S, Dantanarayana A, Delgado P, May JA, Dean T, Christianson DW: Structural analysis of inhibitor binding to human carbonic anhydrase II. Protein Sci. 1998 Dec;7(12):2483-9. [Article]
- Ilies M, Supuran CT, Scozzafava A, Casini A, Mincione F, Menabuoni L, Caproiu MT, Maganu M, Banciu MD: Carbonic anhydrase inhibitors: sulfonamides incorporating furan-, thiophene- and pyrrole-carboxamido groups possess strong topical intraocular pressure lowering properties as aqueous suspensions. Bioorg Med Chem. 2000 Aug;8(8):2145-55. [Article]
- Iester M: Brinzolamide ophthalmic suspension: a review of its pharmacology and use in the treatment of open angle glaucoma and ocular hypertension. Clin Ophthalmol. 2008 Sep;2(3):517-23. [Article]
- Vullo D, Franchi M, Gallori E, Antel J, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides. J Med Chem. 2004 Feb 26;47(5):1272-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
- Gene Name
- CA1
- Uniprot ID
- P00915
- Uniprot Name
- Carbonic anhydrase 1
- Molecular Weight
- 28870.0 Da
References
- Winum JY, Casini A, Mincione F, Starnotti M, Montero JL, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: N-(p-sulfamoylphenyl)-alpha-D-glycopyranosylamines as topically acting antiglaucoma agents in hypertensive rabbits. Bioorg Med Chem Lett. 2004 Jan 5;14(1):225-9. [Article]
- Herkel U, Pfeiffer N: Update on topical carbonic anhydrase inhibitors. Curr Opin Ophthalmol. 2001 Apr;12(2):88-93. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina an...
- Gene Name
- CA4
- Uniprot ID
- P22748
- Uniprot Name
- Carbonic anhydrase 4
- Molecular Weight
- 35032.075 Da
References
- Vullo D, Franchi M, Gallori E, Antel J, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides. J Med Chem. 2004 Feb 26;47(5):1272-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Reversible hydration of carbon dioxide. Low activity.
- Gene Name
- CA5A
- Uniprot ID
- P35218
- Uniprot Name
- Carbonic anhydrase 5A, mitochondrial
- Molecular Weight
- 34750.21 Da
References
- Vullo D, Franchi M, Gallori E, Antel J, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides. J Med Chem. 2004 Feb 26;47(5):1272-9. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Zinc ion binding
- Specific Function
- Reversible hydration of carbon dioxide.
- Gene Name
- CA3
- Uniprot ID
- P07451
- Uniprot Name
- Carbonic anhydrase 3
- Molecular Weight
- 29557.215 Da
References
- Nishimori I, Minakuchi T, Onishi S, Vullo D, Cecchi A, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: cloning, characterization, and inhibition studies of the cytosolic isozyme III with sulfonamides. Bioorg Med Chem. 2007 Dec 1;15(23):7229-36. Epub 2007 Aug 25. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [Article]
- Australian Government: Public Assessment Report for Brinzolamide/ Timolol Maleate [Link]
- EMA Approved Drug Products: SIMBRINZA (brinzolamide and brimonidine tartrate ophthalmic suspension) 1%/0.2@ for topical opththalmic use (May 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
- Gene Name
- CYP2A6
- Uniprot ID
- P11509
- Uniprot Name
- Cytochrome P450 2A6
- Molecular Weight
- 56501.005 Da
References
- EMA Approved Drug Products: SIMBRINZA (brinzolamide and brimonidine tartrate ophthalmic suspension) 1%/0.2@ for topical opththalmic use (May 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- EMA Approved Drug Products: SIMBRINZA (brinzolamide and brimonidine tartrate ophthalmic suspension) 1%/0.2@ for topical opththalmic use (May 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- EMA Approved Drug Products: SIMBRINZA (brinzolamide and brimonidine tartrate ophthalmic suspension) 1%/0.2@ for topical opththalmic use (May 2023) [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- EMA Approved Drug Products: SIMBRINZA (brinzolamide and brimonidine tartrate ophthalmic suspension) 1%/0.2@ for topical opththalmic use (May 2023) [Link]
Drug created at June 13, 2005 13:24 / Updated at February 20, 2024 23:55