| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| Targets |
Carbonic anhydrase II (CA II) (IC50 = 3.2 nM); aqueous humor secretion; intraocular pressure.
|
|---|---|
| ln Vitro |
Brinzolamide hydrochloride is a highly potent CA II inhibitor with an IC50 of 3.2 nM. It shows selectivity for CA II over CA I and other isoforms, which limits systemic carbonic anhydrase inhibition at therapeutic ocular doses. It reduces bicarbonate and aqueous humor formation in the ciliary epithelium, producing a sustained decrease in intraocular pressure after topical administration.
|
| ln Vivo |
In individuals with normotension, brinzolamide hydrochloride (7.5 mg or 12 mg) implanted in a silicone matrix is well tolerated, releases brinzolamide sustainably, and dramatically reduces intraocular pressure (IOP) for up to 28 days. NZW rabbits did not exhibit any harmful responses or symptoms [2]. Characteristics of brinzolamide hydrochloride pharmacokinetics in rabbits [1]. 4.5 mg administered intracamerally 4.5 mg administered intracamerally Administration locally (500 mg) Administration locally (500 mg) parameters for PK Iris-ciliary body aqueous humor Iris-ciliary body aqueous humor 0.08 0.5 1 0.25 Cmax (ng/mL, ng/g) Tmax (h) 4,08 1245 11,050 1964 408 Point of termination t1/2 (h) 3.4 13 2 13.6 (h*ng/mL, h*ng/g) AUC0-24h AUC0 -∞ (h*ng/mL), h*ng/g) = 17,780 7725 1896 11414 17,836 8839 1955 1662 Normalized AUC0-∞ for Dose (h*/mL, h*/g) 4 2 = 0.004 = 0.03
In vivo, topical brinzolamide hydrochloride (1% suspension, one drop two to three times daily) lowers intraocular pressure in patients with glaucoma or ocular hypertension by 15–20%. Systemic absorption is low, but oral or intravenous exposure can produce diuresis and metabolic acidosis through renal CA II inhibition. |
| Enzyme Assay |
For CA II inhibition, purified human CA II is incubated with 4-nitrophenyl acetate or a fluorescent sulfonamide probe and serially diluted brinzolamide hydrochloride (0.01 nM–10 μM) in assay buffer. Esterase activity is measured at 400 nm, or probe displacement is measured by fluorescence polarization, and IC50 is derived.
|
| Cell Assay |
For cell-based assays, ciliary epithelial cells or CA II-expressing cell lines are treated with brinzolamide hydrochloride (0.1 nM–10 μM), and CA II activity is measured by a colorimetric esterase assay or by bicarbonate flux. Aqueous humor secretion can be assessed in isolated ciliary body preparations.
|
| Animal Protocol |
Animal/Disease Models: Rabbit[2]
Doses: 7.5 mg, 12 mg Route of Administration: Implant placement Experimental Results: On days 10-28, at a concentration of 12 mg, intraocular pressure was Dramatically diminished by 4.6 mmHg. For in vivo studies, normotensive or glaucomatous rabbits, dogs, or monkeys receive topical brinzolamide hydrochloride (1% suspension, 1–2 drops) in one eye, and intraocular pressure is measured by tonometry at 0–12 h post-dose. Aqueous humor bicarbonate and CA II activity are measured in perfusates, and plasma drug levels are quantified by LC-MS/MS to assess systemic exposure. |
| References |
|
| Molecular Formula |
C12H21N3O5S3.HCL
|
|---|---|
| Molecular Weight |
419.96818
|
| Exact Mass |
419.041
|
| CAS # |
150937-43-2
|
| Related CAS # |
Brinzolamide;138890-62-7;Brinzolamide-d5 hydrochloride
|
| PubChem CID |
11711447
|
| Appearance |
Typically exists as solid at room temperature
|
| Boiling Point |
586ºC at 760 mmHg
|
| Flash Point |
308.2ºC
|
| Vapour Pressure |
1.03E-13mmHg at 25°C
|
| LogP |
4.079
|
| tPSA |
163.8
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
24
|
| Complexity |
598
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
Cl.COCCCN1C[C@H](NCC)C2C=C(SC=2S1(=O)=O)S(=O)(N)=O
|
| InChi Key |
UGAMYTZPFRXCOG-PPHPATTJSA-N
|
| InChi Code |
InChI=1S/C12H21N3O5S3.ClH/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);1H/t10-;/m0./s1
|
| Chemical Name |
(4R)-4-(ethylamino)-2-(3-methoxypropyl)-1,1-dioxo-3,4-dihydrothieno[3,2-e]thiazine-6-sulfonamide;hydrochloride
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3811 mL | 11.9056 mL | 23.8112 mL | |
| 5 mM | 0.4762 mL | 2.3811 mL | 4.7622 mL | |
| 10 mM | 0.2381 mL | 1.1906 mL | 2.3811 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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