体外活性：Camostat (30 μM) 可以延长人气道上皮细胞模型中 ENaC 功能的衰减，这种衰减在添加过量胰蛋白酶后是可逆的。 Camostat mesilate (500 mM) 通过抑制纤溶酶活性来抑制 TGF-β 的生成，并降低 TGF-β 的活性，从而阻断 HSC 的体外激活。甲磺酸卡莫司他 (20 mM) 与胰岛素联合可在大肠给药后产生显着的降血糖作用。 Camostat mesilate (20 mM) 可有效减少大鼠小肠和大肠匀浆中的胰岛素降解。 Camostat mesilate (2 mM) 抑制激活的大鼠单核细胞中 MCP-1 和 TNF 的产生。 Camostat mesilate (2 mM) 抑制培养的大鼠 PSC 的增殖和 MCP-1 的产生。

Camostat（100 μg/kg it）可诱导豚鼠气管中 ENaC 活性的有效且持久的减弱。卡莫司他甲磺酸盐（1-2 mg/g 饮食）可显着减弱猪血清治疗大鼠肝纤溶酶和 TGF-β 水平的增加、HSC 活化和肝纤维化，而没有明显的全身或局部副作用。卡莫司他甲磺酸盐 (1 mg/g) 可预防 DBTC 诱导的大鼠慢性胰腺炎的胰腺萎缩并改善胰腺外分泌功能。 Camostat mesilate (1 mg/g) 抑制 DBTC 诱导的慢性炎症和胰腺纤维化。 Camostat mesilate (1 mg/g) 抑制 DBTC 诱导的胰腺纤维化的发展和 PSC 的活化。 Camostat mesilate (1 mg/g) 抑制单核细胞浸润并抑制血清和胰腺组织中的 MCP-1 表达。甲磺酸卡莫司他（100 mg/kg）显着增加慢性胰腺炎大鼠的体重和胰腺湿重，并通过抑制PAP、p8和细胞因子的基因表达，显着抑制胰腺的炎症变化和纤维化。

Absorption, Distribution and Excretion
A 200mg oral dose of camostat mesylate leads to the active metabolite reaching a Cmax of 87.1 ± 29.5 ng/mL, with a Tmax of 40 min, and an AUC of 10,400 ± 1,400 ng\*min/mL.
Camostat mesylate is 89.8-95.6% eliminated in the urine and 1.0-1.7% eliminated in the feces.
The volume of distribution at steady state of camostat mesylate is 0.34-1.31L/kg.
The clearance of camostat mesylate is 4.5-7.3mL/min/kg.

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Metabolism / Metabolites
Camostat mesylate is hydrolyzed by carboxyesterate to the active 4-(4-guanidinobenzoyloxy) phenylacetate. The active metabolite is further hydrolyzed by arylesterase to 4-guanidinobenzoic acid.

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Biological Half-Life
The half life of camostat mesylate is 3.8-4.7h.

Protein Binding
Camostat mesylate is 25.8-28.2% protein bound to human serum proteins _in vitro_.

Camostat is a benzoate ester resulting from the formal condensation of the carboxy group of 4-guanidinobenzoic acid with the hydroxy group of 2-(dimethylamino)-2-oxoethyl (4-hydroxyphenyl)acetate. It is a potent inhibitor of the human transmembrane protease serine 2 (TMPRSS2) and its mesylate salt is currently under investigation for its effectiveness in COVID-19 patients. It has a role as an anticoronaviral agent, a serine protease inhibitor, an antifibrinolytic drug, an anti-inflammatory agent, an antiviral agent, an antihypertensive agent and an antineoplastic agent. It is a tertiary carboxamide, a carboxylic ester, a diester, a member of guanidines and a benzoate ester. It is functionally related to a 4-guanidinobenzoic acid. It is a conjugate base of a camostat(1+).
Camostat mesylate, or FOY-305, is a synthetic serine protease inhibitor. It was first described in the literature in 1981, as part of research on the inhibition of skin tumors in mice. Camostat mesylate inhibits cholecystokinin, pro-inflammatory cytokines, and serine proteases, leading to it being investigated for multiple indications including the treatment of COVID-19. Camostat mesylate was first approved in Japan in January 2006.
Camostat is an orally bioavailable, synthetic serine protease inhibitor, with anti-inflammatory, antifibrotic, and potential antiviral activities. Upon oral administration, camostat and its metabolite 4-(4-guanidinobenzoyloxyl)phenyl acetic acid (FOY 251) inhibit the activities of a variety of proteases, including trypsin, kallikrein, thrombin and plasmin, and C1r- and C1 esterases. Although the mechanism of action of camostat is not fully understood, trypsinogen activation in the pancreas is known to be a trigger reaction in the development of pancreatitis. Camostat blocks the activation of trypsinogen to trypsin and the inflammatory cascade that follows. Camostat may also suppress the expression of the cytokines interleukin-1beta (IL-1b), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and transforming growth factor-beta (TGF-beta), along with alpha-smooth muscle actin (alpha-SMA). This reduces inflammation and fibrosis of the pancreas. In addition, camostat may inhibit the activity of transmembrane protease, serine 2 (TMPRSS2), a host cell serine protease that mediates viral cell entry for influenza virus and coronavirus, thereby inhibiting viral infection and replication.

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Drug Indication
Camostat mesylate is indicated in Japan to treat chronic pancreatitis and drug induced lung injury. It is also being investigated as a potential treatment for COVID-19.

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Mechanism of Action
In rats, oral camostat mesylate may increase pancreatic secretions and hypertrophy by increasing cholecystokinin release. Administration in rats has also lead to lower levels of IL-1beta, IL-6, TNF-alpha, TGF-beta, and PSC. Similar activity is seem after administration in humans, leading to reduced pain and inflammation as well as improve the function of the pancrease in chronic pancreatitis. In the case of SARS-CoV-2, camostat mesylate inhibits the action of the serine protease TMPRSS2, preventing the priming of the viral spike protein for attachment to ACE2, and entry into the cell.

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Pharmacodynamics
Camostat mesylate is a protease inhibitor used to treat chronic pancreatitis. The duration of action is not long, as it is typically given in 3 divided doses daily. Patients should be counselled regarding the risk of anaphylaxis, thrombocytopenia, hepatic dysfunction, and hyperkalemia.

C21H26N4O8S

494.519

398.159

59721-28-7

59721-29-8 (mesylate);59721-28-7;

2536

Typically exists as solid at room temperature

1.3±0.1 g/cm3

634.6±65.0 °C at 760 mmHg

194-198ºC

337.6±34.3 °C

0.0±1.9 mmHg at 25°C

1.597

1.29

134.81

2

6

9

29

602

0

O=C(OC1=CC=C(CC(OCC(N(C)C)=O)=O)C=C1)C2=CC=C(NC(N)=N)C=C2

XASIMHXSUQUHLV-UHFFFAOYSA-N

InChI=1S/C20H22N4O5/c1-24(2)17(25)12-28-18(26)11-13-3-9-16(10-4-13)29-19(27)14-5-7-15(8-6-14)23-20(21)22/h3-10H,11-12H2,1-2H3,(H4,21,22,23)

[4-[2-[2-(dimethylamino)-2-oxoethoxy]-2-oxoethyl]phenyl] 4-(diaminomethylideneamino)benzoate

FOY 305 Synonym

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
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。