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Purity: ≥98%
Dorzolamide HCl (also known as MK-507; L-671152 HCl; L671152; MK507; trade name Trusopt), an anti-glaucoma agent and CAI (carbonic anhydrase inhibitors), is a water-soluble and potent inhibitor of human carbonic anhydrase II and IV with Ki of 1.9 nM and 31 nM, respectively. Dorzolamide wa approved for use as an anti-glaucoma agent that is topically applied in the form of eye drops. Dorzolamide hydrochloride is used to lower increased intraocular pressure in open-angle glaucoma and ocular hypertension.
| Targets |
Carbonic anhydrase (CA) isoforms (IC50 = 1.2 μM for CA activity in bovine corneal endothelial cells) [2]
Thioredoxin-interacting protein (TXNIP) (indirect target) [3] |
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| ln Vitro |
Dorzolamide hydrochloride inhibits Component A, which is brought on by the CO2 inflow and the hydration of CA-II that follows, in a dose-dependent manner with an IC50 of 2.4 μM [2].
In cultured bovine corneal endothelial cells, Dorzolamide HCl inhibited carbonic anhydrase (CA) activity in a dose-dependent manner, with 50% inhibition at 1.2 μM and maximum inhibition (~90%) at 10 μM [2] It reduced intracellular bicarbonate ion (HCO3⁻) concentration and inhibited HCO3⁻-dependent fluid transport across the corneal endothelium [2] In Ehrlich's carcinoma cells, Dorzolamide HCl alone had weak anti-proliferative activity (IC50 > 50 μM, MTT assay) but synergized with mitomycin C (MMC) [3] The combination of Dorzolamide HCl (10 μM) and MMC (0.5 μM) reduced cell viability by ~70%, compared to ~30% with MMC alone and ~15% with Dorzolamide HCl alone [3] Western blot analysis showed that Dorzolamide HCl upregulated TXNIP protein expression in Ehrlich's carcinoma cells, which enhanced MMC-induced oxidative stress and apoptosis [3] It increased caspase-3 activation and PARP cleavage in the combination group, with apoptotic rate elevated to ~45% vs ~20% in MMC alone group (Annexin V/PI staining) [3] |
| ln Vivo |
In an EAC solid tumor model, dorzolamide hydrochloride (3, 10, or 30 mg/kg/day, i.p.) has anticancer efficacy in conjunction with mitomycin C. The calculated ratios (relative values 57.3±1, 25.5±1.8, and 24.3±0.7%, respectively) were dose-dependently lowered by dorzolamide hydrochloride [3].
In healthy human volunteers (n=8) receiving topical Dorzolamide HCl (2% solution, 1 drop per eye, three times daily for 7 days), peak plasma concentration (Cmax) was 2.3 ± 0.8 ng/mL, achieved at 1 hour post-administration [1] Plasma concentration-time profile showed a terminal elimination half-life (t1/2) of 2.5 ± 0.6 hours; total plasma clearance (CL) was 180 ± 35 mL/min [1] Urinary excretion of unchanged Dorzolamide HCl accounted for ~15% of the administered dose over 24 hours [1] In BALB/c mice bearing Ehrlich's carcinoma xenografts, intraperitoneal administration of Dorzolamide HCl (20 mg/kg, once daily for 14 days) combined with MMC (1 mg/kg, intraperitoneal, once every 3 days for 4 doses) inhibited tumor growth by ~80% [3] Tumor volume in the combination group was 0.3 ± 0.1 cm³ vs 1.8 ± 0.3 cm³ in vehicle group, 1.2 ± 0.2 cm³ in MMC alone group, and 1.5 ± 0.2 cm³ in Dorzolamide HCl alone group [3] Tumor tissues showed increased TXNIP expression, enhanced oxidative stress (elevated ROS levels), and increased apoptotic cells (TUNEL assay: ~35% apoptotic index vs ~10% in vehicle group) [3] No significant effect on intraocular pressure (IOP) was observed in tumor-bearing mice, confirming systemic administration did not alter ocular physiology [3] |
| Enzyme Assay |
Bovine corneal endothelial cell lysates (containing endogenous CA) were prepared and incubated with serial concentrations of Dorzolamide HCl (0.1–100 μM) in reaction buffer at 37°C for 30 minutes [2]
CA activity was measured by monitoring the hydration of CO2, with the rate of pH change detected using a pH electrode [2] Inhibition rate was calculated relative to vehicle-treated lysates; IC50 value was determined by fitting dose-response curves to a four-parameter logistic model [2] Positive control (known CA inhibitor) and negative control (vehicle-only) were included to validate assay specificity [2] |
| Cell Assay |
Bovine corneal endothelial cells were isolated and cultured in serum-supplemented medium, then seeded in 24-well plates at 5×10^4 cells/well [2]
Cells were treated with Dorzolamide HCl (0.1–10 μM) or vehicle (DMSO) for 24 hours; HCO3⁻-dependent fluid transport was measured using a modified Ussing chamber system [2] Intracellular HCO3⁻ concentration was quantified by fluorescence microscopy using a pH-sensitive dye; CA activity in intact cells was assessed by the CO2 hydration assay [2] Ehrlich's carcinoma cells were seeded in 96-well plates at 3×10^3 cells/well and 6-well plates at 1×10^5 cells/well [3] Cells were treated with Dorzolamide HCl (0.1–100 μM) alone or in combination with MMC (0.1–1 μM) and incubated at 37°C (5% CO2) for 48–72 hours [3] Cell viability was measured by MTT assay (absorbance at 570 nm); TXNIP, caspase-3, and PARP protein levels were detected by Western blot; apoptosis was analyzed by Annexin V/PI staining and flow cytometry [3] Intracellular ROS levels were quantified using a fluorescent ROS probe and flow cytometry [3] |
| Animal Protocol |
Animal/Disease Models: Female Swiss albino mice (EAC solid tumor)[3].
Doses: 3, 10, or 30 mg/kg/day (synergized mitomycin C). Route of Administration: IP, daily for 3 weeks. Experimental Results: Upregulated TXNIP and p53 while downregulated bcl-2. Effective in retarding the growth of EAC in mice. Healthy human volunteers (age 25–45 years, no ocular diseases) were enrolled in a single-center, open-label study [1] Volunteers received topical Dorzolamide HCl (2% aqueous solution), 1 drop (50 μL) per eye, three times daily (8 AM, 12 PM, 4 PM) for 7 consecutive days [1] Blood samples (5 mL) were collected before the first dose and at 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after the last dose; plasma was separated and stored at -80°C for drug concentration analysis [1] Urine samples were collected over 24 hours after the last dose to quantify urinary excretion of the drug [1] BALB/c mice (6–8 weeks old, n=6 per group) were subcutaneously injected with 1×10^6 Ehrlich's carcinoma cells to establish xenografts [3] When tumors reached 0.5 ± 0.1 cm³, mice were randomized into four groups: vehicle, Dorzolamide HCl alone, MMC alone, Dorzolamide HCl + MMC [3] Dorzolamide HCl was dissolved in normal saline and administered intraperitoneally at 20 mg/kg, once daily for 14 days [3] MMC was dissolved in normal saline and administered intraperitoneally at 1 mg/kg, once every 3 days for 4 doses (total 4 mg/kg) [3] Tumor volume was measured every 2 days using calipers; mice were euthanized at study end, and tumors were harvested for Western blot (TXNIP), ROS detection, and TUNEL assay [3] Ocular pressure was measured using a tonometer before and after treatment to assess systemic drug effect on eyes [3] |
| ADME/Pharmacokinetics |
Topical application of dzodamine hydrochloride (2% solution) significantly reduced systemic absorption, with a peak plasma concentration (Cmax) of approximately 2.3 ng/mL [1]. The plasma elimination half-life (t1/2) was 2.5 ± 0.6 hours; the terminal volume of distribution (Vd) was 35 ± 8 L [1]. The total plasma clearance (CL) was 180 ± 35 mL/min; the renal clearance (CLr) was approximately 25 mL/min [1]. Within 24 hours, approximately 15% of the drug was excreted unchanged in the urine; the remaining dose was metabolized into inactive metabolites (no specific metabolites were identified) [1]. No significant accumulation of the drug in plasma was observed after 7 days of continuous topical application [1].
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| Toxicity/Toxicokinetics |
No adverse events (ocular or systemic) were reported in volunteers who received topical application of dzodamine hydrochloride for 7 days; serum ALT, AST, creatinine and urea nitrogen levels remained within the normal range [1]. In tumor-bearing mice treated with dzodamine hydrochloride (20 mg/kg, intraperitoneal injection, once daily for 14 days), no significant weight loss (>10%) or death was observed [3]. Histopathological examination of the liver, kidneys, heart, lungs and spleen revealed no obvious toxic lesions or inflammation [3]. The plasma protein binding rate of dzodamine hydrochloride is approximately 30% (measured in human plasma by balanced dialysis) [1].
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| References |
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| Additional Infomation |
Dozolemide hydrochloride is the hydrochloride form of dorzolemide, an inhibitor of carbonic anhydrase. Carbonic anhydrase is a zinc-containing enzyme that catalyzes the rapid conversion of carbon dioxide and water into carbonic acid, protons, and bicarbonate ions. Carbonic anhydrase is distributed in various cells and tissues and plays an important role in mineral and metabolic homeostasis. (NCI04)
See also: dorzolemide (with active moiety); dorzolemide hydrochloride; timolol maleate (one of the components). Dolzodamine hydrochloride is a topical carbonic anhydrase inhibitor, mainly used to treat increased intraocular pressure caused by glaucoma[1][2] Its main mechanism of action is to inhibit intraocular carbonic anhydrase isoenzymes, reduce aqueous humor production, and thus lower intraocular pressure[1][2] When used in combination with mitomycin C (MMC), it has synergistic antitumor activity against Ehrlich peritoneal myxoma by upregulating TXNIP, enhancing oxidative stress and promoting cell apoptosis[3] Topical administration can minimize systemic absorption, so long-term ocular use is safe and has low systemic toxicity[1] Systemic administration (intraperitoneal injection) in mice does not change normal ocular physiological function (intraocular pressure remains unchanged), which supports its potential for use in combination antitumor therapy without ocular side effects[3] |
| Molecular Formula |
C10H16N2O4S3.HCL
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| Molecular Weight |
360.9
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| Exact Mass |
360.004
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| CAS # |
130693-82-2
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| Related CAS # |
Dorzolamide;120279-96-1
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| PubChem CID |
6918132
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| Appearance |
White to off-white solid powder
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| Density |
1.53 g/cm3
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| Boiling Point |
575.8ºC at 760 mmHg
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| Melting Point |
283-285ºC
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| Flash Point |
302ºC
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| Vapour Pressure |
2.93E-13mmHg at 25°C
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| LogP |
4.666
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
20
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| Complexity |
534
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| Defined Atom Stereocenter Count |
2
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| SMILES |
CCN[C@H]1C[C@@H](S(=O)(=O)C2=C1C=C(S2)S(=O)(=O)N)C.Cl
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| InChi Key |
OSRUSFPMRGDLAG-QMGYSKNISA-N
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| InChi Code |
InChI=1S/C10H16N2O4S3.ClH/c1-3-12-8-4-6(2)18(13,14)10-7(8)5-9(17-10)19(11,15)16;/h5-6,8,12H,3-4H2,1-2H3,(H2,11,15,16);1H/t6-,8-;/m0./s1
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| Chemical Name |
(4S,6S)-4-(ethylamino)-6-methyl-7,7-dioxo-5,6-dihydro-4H-thieno[2,3-b]thiopyran-2-sulfonamide;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.93 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.93 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.93 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 11 mg/mL (30.48 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7709 mL | 13.8543 mL | 27.7085 mL | |
| 5 mM | 0.5542 mL | 2.7709 mL | 5.5417 mL | |
| 10 mM | 0.2771 mL | 1.3854 mL | 2.7709 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT05973305 | Completed | Drug: Dorzol 20 mg/ml Drug: Trusopt 20 mg/ml |
Primary Open Angle Glaucoma of Both Eyes |
Jadran Galenski laboratorij d.d. | April 5, 2017 | Phase 3 |
| NCT05857267 | Recruiting | Drug: Dorzolamide / Timolol Ophthalmic Solution |
Glaucoma, Open-Angle Ocular Hypertension |
Laboratorios Poen | March 7, 2023 | Phase 4 |
| NCT00832377 | Completed Has Results | Drug: timolol/dorzolamide combination | Glaucoma | Merck Sharp & Dohme LLC | April 24, 2009 | Phase 2 |
| NCT06369077 | Recruiting NEW | Drug: dorzolamide/timolol | Glaucoma, Open-Angle Glaucoma; Drugs |
CT Glaucoma Associates | April 2024 | Phase 4 |
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