Brinzolamide

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
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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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to manageElevated intraocular pressureCombination Product in combination with: Timolol (DB00373)•••••••••••••••••••••• •••••••• •• •••••••••••••••••••••• •••••••••• • •••••
Used in combination to manageElevated intraocular pressureCombination Product in combination with: Timolol (DB00373)•••••••••••••••••••••• •••••••• •• •••••••••••••••••••••• •••••••••• • •••••
Treatment ofIncreased intra ocular pressure (iop)••••••••••••••••••••••• •••••••••• • •••••
Used in combination to treatIncreased intra ocular pressure (iop)Combination Product in combination with: Brimonidine (DB00484)••••••••••••••••••••••• •••••••••• • •••••
Treatment ofIncreased intra ocular pressure (iop)••••••••••••••••••••••• •••••••••• • •••••
Contraindications & Blackbox Warnings
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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

TargetActionsOrganism
ACarbonic anhydrase 2
inhibitor
Humans
UCarbonic anhydrase 1
inhibitor
Humans
UCarbonic anhydrase 4
inhibitor
Humans
UCarbonic anhydrase 5A, mitochondrial
inhibitor
Humans
UCarbonic anhydrase 3
inhibitor
Humans
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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Toxicity

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
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AbametapirThe serum concentration of Brinzolamide can be increased when it is combined with Abametapir.
AcetazolamideThe risk or severity of adverse effects can be increased when Brinzolamide is combined with Acetazolamide.
Acetylsalicylic acidThe risk or severity of electrolyte abnormality can be increased when Brinzolamide is combined with Acetylsalicylic acid.
Aminosalicylic acidThe risk or severity of electrolyte abnormality can be increased when Brinzolamide is combined with Aminosalicylic acid.
ApalutamideThe serum concentration of Brinzolamide can be decreased when it is combined with Apalutamide.
Food Interactions
No interactions found.

Products

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Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AzoptSuspension / drops10 mg/mlOphthalmicNovartis Europharm Limited2020-12-17Not applicableEU flag
AzoptSuspension / drops10 mg/1mLOphthalmicALCON LABORATORIES, INC.1998-04-30Not applicableUS flag
AzoptSuspension / drops10 mg/1mLOphthalmicNovartis Pharmaceuticals Corporation1998-04-30Not applicableUS flag
AzoptSuspension / drops10 mg/mlOphthalmicNovartis Europharm Limited2020-12-17Not applicableEU flag
AzoptSuspension1 % w/vOphthalmicNovartis1998-11-11Not applicableCanada flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
BrinzolamideSuspension / drops10 mg/1mLOphthalmicPadagis US LLC2023-10-10Not applicableUS flag
BrinzolamideSuspension / drops10 mg/1mLOphthalmicbryant ranch prepack2021-03-08Not applicableUS flag
BrinzolamideSuspension / drops10 mg/1mLOphthalmicActavis Pharma, Inc.2021-03-08Not applicableUS flag
BrinzolamideSuspension / drops10 mg/1mLOphthalmicBausch & Lomb Incorporated2022-03-31Not applicableUS flag
BrinzolamideSuspension / drops10 mg/1mLOphthalmicOceanside Pharmaceuticals.2021-08-25Not applicableUS flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
AzargaBrinzolamide (1 % w/v) + Timolol maleate (0.5 % w/v)SuspensionOphthalmicNovartis2009-08-25Not applicableCanada flag
AZARGABrinzolamide (10 mg/mL) + Timolol maleate (5 mg/mL)Solution / drops; Suspension / dropsOphthalmic2017-01-01Not applicableGermany flag
AZARGABrinzolamide (10 mg/mL) + Timolol maleate (5 mg/mL)Solution / drops; Suspension / dropsOphthalmic2017-01-01Not applicableGermany flag
AZARGABrinzolamide (10 mg/mL) + Timolol maleate (5 mg/mL)Solution / drops; Suspension / dropsOphthalmic2017-01-01Not applicableGermany flag
AZARGABrinzolamide (10 mg/mL) + Timolol maleate (5 mg/mL)Solution / drops; Suspension / dropsOphthalmic2017-01-01Not applicableGermany flag

Categories

ATC Codes
S01EC54 — Brinzolamide, combinationsS01EC04 — BrinzolamideG01AE10 — Combinations of sulfonamides
Drug Categories
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
  1. 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]
  2. 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]
  3. 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]
  4. DeSantis L: Preclinical overview of brinzolamide. Surv Ophthalmol. 2000 Jan;44 Suppl 2:S119-29. [Article]
  5. FDA Approved Drug Products: AZOPT (brinzolamide) suspension [Link]
  6. FDA Approved Drug Products: SIMBRINZA (brinzolamide and brimonidine tartrate) suspension [Link]
  7. EMA Product Information: AZARGA (brinzolamide and timolol maleate) suspension [Link]
  8. FDA Approved Drug Products: SIMBRINZA (brinzolamide and brimonidine tartrate ophthalmic suspension) 1%/0.2%, for topical ophthalmic use (May 2023) [Link]
  9. Brinzolamide MSDS [Link]
  10. EMA Approved Drug Products: SIMBRINZA (brinzolamide and brimonidine tartrate ophthalmic suspension) 1%/0.2@ for topical opththalmic use (May 2023) [Link]
  11. EMA Approved Drug Products: AZOPT (brinzolamide) suspension [Link]
Human Metabolome Database
HMDB0015325
KEGG Drug
D00652
KEGG Compound
C07760
PubChem Compound
68844
PubChem Substance
46507071
ChemSpider
62077
BindingDB
10885
RxNav
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
PhaseStatusPurposeConditionsCount
4CompletedNot AvailableOcular Hypertension / Open Angle Glaucoma (OAG)1
4CompletedPreventionOcular Hypertension / Posterior Capsule Opacification1
4CompletedTreatmentGlaucoma11
4CompletedTreatmentGlaucoma / Ocular Hypertension6
4CompletedTreatmentGlaucoma / Ocular Hypertension / Open Angle Glaucoma (OAG)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Alcon Laboratories
Dosage Forms
FormRouteStrength
Solution / dropsOphthalmic
Solution / drops; suspension / dropsOphthalmic
SuspensionOphthalmic10 mg/mL
Solution / dropsOphthalmic
SuspensionOphthalmic1 % w/v
Suspension / dropsOphthalmic10 mg/1mL
Solution / drops; suspension / dropsOphthalmic10 MG/ML
SuspensionOphthalmic
SuspensionOphthalmic10 MG/ML
SolutionOphthalmic10 mg/ml
SuspensionConjunctival; Ophthalmic10 mg
SuspensionOphthalmic10.000 mg
Solution / dropsOphthalmic10 MG/ML
Suspension / dropsOphthalmic10 mg/ml
PowderNot applicable25 kg/1
Solution / dropsOphthalmic1 %
SuspensionOphthalmic1 %
SuspensionOphthalmic
Suspension / dropsOphthalmic
Prices
Unit descriptionCostUnit
Azopt 1% Suspension 15ml Bottle163.11USD bottle
Azopt 1% Suspension 10ml Bottle108.83USD bottle
Azopt 1% eye drops8.05USD ml
Azopt 1 % Suspension3.63USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5461081No1995-10-242013-04-24US flag
US5240923No1993-08-312010-08-31US flag
CA2080223No2000-11-072011-04-03Canada flag
US6316441No2001-11-132019-12-07US flag
US9044484No2015-06-022030-10-30US flag
US9421265No2016-08-232030-06-17US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)131 - 132 °CL46382
Predicted Properties
PropertyValueSource
Water Solubility0.713 mg/mLALOGPS
logP-0.65ALOGPS
logP-0.58Chemaxon
logS-2.7ALOGPS
pKa (Strongest Acidic)8.18Chemaxon
pKa (Strongest Basic)6.5Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area118.8 Å2Chemaxon
Rotatable Bond Count7Chemaxon
Refractivity87.2 m3·mol-1Chemaxon
Polarizability37.93 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9765
Blood Brain Barrier+0.8754
Caco-2 permeable-0.7123
P-glycoprotein substrateSubstrate0.8185
P-glycoprotein inhibitor INon-inhibitor0.6795
P-glycoprotein inhibitor IINon-inhibitor0.9245
Renal organic cation transporterNon-inhibitor0.8276
CYP450 2C9 substrateNon-substrate0.7897
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6431
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8588
Ames testNon AMES toxic0.5982
CarcinogenicityNon-carcinogens0.7712
BiodegradationNot ready biodegradable0.9834
Rat acute toxicity2.4930 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7097
hERG inhibition (predictor II)Non-inhibitor0.5167
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0aor-9363000000-c2ce0727d8312538cab4
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-000i-3940000000-29878662225bb11586ed
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-3940000000-29878662225bb11586ed
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0009000000-d4697bebfc2b62067374
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0009000000-bf5dcee878a2bceb4731
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-1019000000-5942e20a823a05bfe3c7
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-001i-0009000000-faba2a7f1ba15f02b4bc
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00l6-0090000000-81c46e465b531dfff531
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-9221000000-19cda1caf638cc786534
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-193.500788
predicted
DarkChem Lite v0.1.0
[M-H]-191.693288
predicted
DarkChem Lite v0.1.0
[M-H]-181.31767
predicted
DeepCCS 1.0 (2019)
[M+H]+194.317388
predicted
DarkChem Lite v0.1.0
[M+H]+192.511888
predicted
DarkChem Lite v0.1.0
[M+H]+183.67567
predicted
DeepCCS 1.0 (2019)
[M+Na]+193.399588
predicted
DarkChem Lite v0.1.0
[M+Na]+192.395188
predicted
DarkChem Lite v0.1.0
[M+Na]+190.96211
predicted
DeepCCS 1.0 (2019)

Targets

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Details
1. Carbonic anhydrase 2
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
  1. 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]
  2. DeSantis L: Preclinical overview of brinzolamide. Surv Ophthalmol. 2000 Jan;44 Suppl 2:S119-29. [Article]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. 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]
Details
2. Carbonic anhydrase 1
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
  1. 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]
  2. Herkel U, Pfeiffer N: Update on topical carbonic anhydrase inhibitors. Curr Opin Ophthalmol. 2001 Apr;12(2):88-93. [Article]
Details
3. Carbonic anhydrase 4
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
  1. 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
  1. 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]
Details
5. Carbonic anhydrase 3
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
  1. 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
  1. 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]
  2. Australian Government: Public Assessment Report for Brinzolamide/ Timolol Maleate [Link]
  3. 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
  1. 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
  1. 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
  1. 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
  1. 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 27, 2024 23:09