| 规格 | 价格 | 库存 | 数量 |
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| 10 mM * 1 mL in DMSO |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| 1g |
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| 靶点 |
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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| 体外研究 (In Vitro) |
Dorzolamide 盐酸盐以剂量依赖性方式抑制由 CO2 流入和随后的 CA-II 水合引起的组分 A，IC50 为 2.4 μM [2]。
在培养的牛角膜内皮细胞中，Dorzolamide HCl呈剂量依赖性抑制碳酸酐酶（CA）活性，1.2 μM时抑制率达50%，10 μM时达到最大抑制率（约90%）[2] 药物降低细胞内碳酸氢根离子（HCO3⁻）浓度，并抑制HCO3⁻依赖的角膜内皮液体转运[2] 在艾氏癌细胞中，Dorzolamide HCl单独使用时抗增殖活性较弱（MTT法IC50>50 μM），但与丝裂霉素C（MMC）具有协同作用[3] Dorzolamide HCl（10 μM）与MMC（0.5 μM）联合处理时，细胞活力降低约70%，而单独MMC组降低约30%，单独Dorzolamide HCl组降低约15%[3] Western blot检测显示，Dorzolamide HCl上调艾氏癌细胞中TXNIP蛋白表达，增强MMC诱导的氧化应激和凋亡[3] 联合组中caspase-3激活和PARP剪切增加，凋亡率升高至约45%，而单独MMC组凋亡率约20%（Annexin V/PI染色）[3] |
| 体内研究 (In Vivo) |
在 EAC 实体瘤模型中，盐酸多佐胺（3、10 或 30 mg/kg/天，腹腔注射）与丝裂霉素 C 联用具有抗癌功效。计算出的比率（相对值 57.3±1、25.5±1.8 和 24.3±盐酸多佐胺可剂量依赖性地降低（分别为 0.7%）[3]。
健康人类志愿者（n=8）局部使用Dorzolamide HCl（2%溶液，每眼1滴，每日3次，连续7天）后，血浆峰值浓度（Cmax）为2.3±0.8 ng/mL，于给药后1小时达到[1] 血浆浓度-时间曲线显示终末消除半衰期（t1/2）为2.5±0.6小时；总血浆清除率（CL）为180±35 mL/min[1] 24小时内原形药物经尿排泄占给药剂量的约15%[1] 在携带艾氏癌异种移植瘤的BALB/c小鼠中，腹腔注射Dorzolamide HCl（20 mg/kg，每日一次，连续14天）联合MMC（1 mg/kg，腹腔注射，每3天一次，共4次），肿瘤生长抑制率约80%[3] 联合组肿瘤体积为0.3±0.1 cm³，而溶媒组为1.8±0.3 cm³，单独MMC组为1.2±0.2 cm³，单独Dorzolamide HCl组为1.5±0.2 cm³[3] 肿瘤组织中TXNIP表达升高，氧化应激增强（ROS水平升高），凋亡细胞增多（TUNEL实验：凋亡指数约35%，溶媒组约10%）[3] 荷瘤小鼠的眼压（IOP）未受显著影响，证实全身给药不会改变眼部生理功能[3] |
| 酶活实验 |
制备牛角膜内皮细胞裂解液（含内源性CA），与系列浓度的Dorzolamide HCl（0.1–100 μM）在反应缓冲液中37°C孵育30分钟[2]
通过监测CO2水合反应速率评估CA活性，利用pH电极检测pH变化[2] 相对于溶媒处理的裂解液计算抑制率，采用四参数logistic模型拟合量效曲线确定IC50值[2] 设置阳性对照（已知CA抑制剂）和阴性对照（仅含溶媒）验证实验特异性[2] |
| 细胞实验 |
分离牛角膜内皮细胞，在含血清培养基中培养，以5×10^4个细胞/孔接种于24孔板[2]
用Dorzolamide HCl（0.1–10 μM）或溶媒（DMSO）处理细胞24小时；采用改良Ussing chamber系统测量HCO3⁻依赖的液体转运[2] 使用pH敏感染料通过荧光显微镜定量细胞内HCO3⁻浓度；通过CO2水合实验评估完整细胞中的CA活性[2] 艾氏癌细胞以3×10^3个细胞/孔接种于96孔板，以1×10^5个细胞/孔接种于6孔板[3] 用Dorzolamide HCl（0.1–100 μM）单独处理或与MMC（0.1–1 μM）联合处理，在37°C、5% CO2条件下孵育48–72小时[3] MTT法检测细胞活力（570 nm吸光度）；Western blot检测TXNIP、caspase-3和PARP蛋白水平；Annexin V/PI染色结合流式细胞术分析凋亡[3] 使用荧光ROS探针和流式细胞术定量细胞内ROS水平[3] |
| 动物实验 |
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] |
| 药代性质 (ADME/PK) |
Topical administration of Dorzolamide HCl (2% solution) results in minimal systemic absorption, with peak plasma concentration (Cmax) of ~2.3 ng/mL in humans [1]
Plasma elimination half-life (t1/2) is 2.5 ± 0.6 hours in humans; terminal phase volume of distribution (Vd) is 35 ± 8 L [1] Total plasma clearance (CL) is 180 ± 35 mL/min; renal clearance (CLr) accounts for ~25 mL/min [1] Urinary excretion of unchanged drug is ~15% of the administered dose over 24 hours; the remaining dose is metabolized to inactive metabolites (no specific metabolites identified) [1] No significant accumulation in plasma was observed after 7 days of repeated topical administration [1] |
| 毒性/毒理 (Toxicokinetics/TK) |
In human volunteers receiving topical Dorzolamide HCl for 7 days, no adverse events (ocular or systemic) were reported; serum ALT, AST, creatinine, and urea nitrogen levels remained within normal ranges [1]
In tumor-bearing mice treated with Dorzolamide HCl (20 mg/kg ip, daily for 14 days), no significant body weight loss (>10%) or mortality was observed [3] Histopathological examination of liver, kidney, heart, lung, and spleen showed no overt toxic lesions or inflammation [3] Plasma protein binding rate of Dorzolamide HCl is ~30% (measured in human plasma via equilibrium dialysis) [1] |
| 参考文献 |
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| 其他信息 |
Dorzolamide Hydrochloride is the hydrochloride salt form of dorzolamide, an inhibitor of carbonic anhydrase, a zinc-containing enzyme that catalyzes the rapid conversion of carbon dioxide and water into carbonic acid, protons and bicarbonate ions. Distributed throughout many cells and tissues, various carbonic anhydrases play important roles in mineral and metabolic homeostasis. (NCI04)
See also: Dorzolamide (has active moiety); Dorzolamide Hydrochloride; Timolol Maleate (component of). Dorzolamide HCl is a topical carbonic anhydrase inhibitor primarily used for the treatment of elevated intraocular pressure (IOP) in glaucoma [1][2] Its primary mechanism involves inhibiting ocular CA isoforms, reducing aqueous humor production and lowering IOP [1][2] It exhibits synergistic antitumor activity with mitomycin C (MMC) in Ehrlich's carcinoma via upregulating TXNIP, enhancing oxidative stress, and promoting apoptosis [3] Topical administration results in minimal systemic absorption, making it safe for long-term ocular use with low systemic toxicity [1] Systemic administration (intraperitoneal) in mice does not alter normal ocular physiology (IOP remains unchanged), supporting its potential for combined antitumor therapy without ocular side effects [3] |
| 分子式 |
C10H16N2O4S3.HCL
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|---|---|---|
| 分子量 |
360.9
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| 精确质量 |
360.004
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| CAS号 |
130693-82-2
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| 相关CAS号 |
Dorzolamide;120279-96-1
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| PubChem CID |
6918132
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| 外观&性状 |
White to off-white solid powder
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| 密度 |
1.53 g/cm3
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| 沸点 |
575.8ºC at 760 mmHg
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| 熔点 |
283-285ºC
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| 闪点 |
302ºC
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| 蒸汽压 |
2.93E-13mmHg at 25°C
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| LogP |
4.666
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| tPSA |
151.33
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| 氢键供体(HBD)数目 |
3
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| 氢键受体(HBA)数目 |
7
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| 可旋转键数目(RBC) |
3
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| 重原子数目 |
20
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| 分子复杂度/Complexity |
534
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| 定义原子立体中心数目 |
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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| 化学名 |
(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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| 别名 |
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| HS Tariff Code |
2934.99.9001
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| 存储方式 |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month 注意： 请将本产品存放在密封且受保护的环境中，避免吸湿/受潮。 |
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| 运输条件 |
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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| 溶解度 (体外实验) |
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| 溶解度 (体内实验) |
配方 1 中的溶解度: ≥ 2.5 mg/mL (6.93 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。 *生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。 配方 2 中的溶解度: ≥ 2.5 mg/mL (6.93 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。 *20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。 View More
配方 3 中的溶解度: ≥ 2.5 mg/mL (6.93 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。 配方 4 中的溶解度: 11 mg/mL (30.48 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶. 1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液)); 2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方): 10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline); 假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL； 3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例; 4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶; 5、为保证最佳实验结果，工作液请现配现用！ 6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们; 7、 以上所有助溶剂都可在 Invivochem.cn网站购买。 |
| 制备储备液 | 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 |
1、根据实验需要选择合适的溶剂配制储备液 (母液)：对于大多数产品，InvivoChem推荐用DMSO配置母液 (比如：5、10、20mM或者10、20、50 mg/mL浓度），个别水溶性高的产品可直接溶于水。产品在DMSO 、水或其他溶剂中的具体溶解度详见上”溶解度 (体外)”部分;
2、如果您找不到您想要的溶解度信息，或者很难将产品溶解在溶液中，请联系我们;
3、建议使用下列计算器进行相关计算（摩尔浓度计算器、稀释计算器、分子量计算器、重组计算器等）;
4、母液配好之后，将其分装到常规用量，并储存在-20°C或-80°C，尽量减少反复冻融循环。
计算结果:
工作液浓度： mg/mL；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL)。如该浓度超过该批次药物DMSO溶解度，请首先与我们联系。
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。
(1) 请确保溶液澄清之后，再加入下一种溶剂 (助溶剂) 。可利用涡旋、超声或水浴加热等方法助溶；
(2) 一定要按顺序加入溶剂 (助溶剂) 。
| 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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