TACE (ADAM17); MMP

体外活性：TAPI-1 可防止单核细胞系 THP-1 和人外周血单核细胞中未刺激和 PMA 诱导的可溶形式 TNF-α、p60 TNFR 和 IL-6R 的释放。 TAPI 还可以抑制 LPS 诱导的单核细胞中 p60 TNFR 和 TNF-α 的脱落。 TAPI-1 抑制共转染 APP 的 TACE 依赖性组成型释放 (695)。 TAPI-1 减弱人 HSC 系 LI90 中 Ang II 诱导的 EGFR 反式激活和细胞增殖。 TAPI-1 与 EGFR 抑制剂 AG1478 表现出 AREG/EGFR/ERK 信号通路失活，并减少 pSS 唾液腺来源的上皮细胞中促炎细胞因子的释放。细胞测定：将 5000 个细胞接种到 96 孔板的每个孔中，并通过 CellTiter-Glo 发光细胞活力测定评估其活力。血清剥夺 24 小时后，用 Ang II 处理细胞 60 小时，并用或不用每种抑制剂和拮抗剂进行预处理。然后将测定底物添加到板上的每个孔中，并使用光度计评估样品。

用 LPS (10 mg/kg, ip) 处理小鼠，并在存在或不存在 1 型 TACE 抑制剂 (1 µM) 或 2 型 TACE 抑制剂的情况下，在有或没有 LPS (10 µg/ml) 的情况下培养 HK-2 细胞（10 µM）。 LPS 治疗导致血清肌酐、TNFα 和尿中性粒细胞明胶酶相关脂质运载蛋白增加。在 LPS 诱导的急性肾损伤和 LPS 处理的 HK-2 细胞中，血管紧张素 II 1 型受体、丝裂原激活蛋白激酶 (MAPK) 和 TACE 表达增加，而血管紧张素转换酶 2 (ACE2) 表达减少。

96 孔板的每个孔含有 5,000 个接种细胞，CellTiter-Glo 发光细胞活力测定用于确定细胞的活力。血清剥夺 24 小时后，细胞接受 Ang II 处理 60 小时，无论有或没有事先抑制剂和拮抗剂预处理。接下来，板上的每个孔都充满测定底物，并使用光度计来评估样品。

Male Sprague-Dawley rats
1 μg
i.c.v.

[1]. J Immunol . 1995 Dec 1;155(11):5198-205.

[2]. Biochem J . 2001 Aug 1;357(Pt 3):787-94.

[3]. Life Sci . 2014 Mar 3;97(2):137-44.

[4]. Clin Exp Med . 2015 May;15(2):215-25.

[5]. Immunobiology . 2020 Mar;225(2):151887.

[6]. Hypertension . 2019 Jul;74(1):63-72.

C26H37N5O5

499.60

499.27946930

171235-71-5

TAPI-1;163847-77-6

Solid

C[C@@H](C(=O)NCCN)NC(=O)[C@H](CC1=CC2=CC=CC=C2C=C1)NC(=O)C(CC(C)C)CC(=O)NO

AWNBSWDIOCXWJW-OWHMDLSXSA-N

InChI=1S/C26H37N5O5/c1-16(2)12-21(15-23(32)31-36)25(34)30-22(26(35)29-17(3)24(33)28-11-10-27)14-18-8-9-19-6-4-5-7-20(19)13-18/h4-9,13,16-17,21-22,36H,10-12,14-15,27H2,1-3H3,(H,28,33)(H,29,35)(H,30,34)(H,31,32)/t17-,21?,22-/m0/s1

N-[(2S)-1-[[(2S)-1-(2-aminoethylamino)-1-oxopropan-2-yl]amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-N'-hydroxy-2-(2-methylpropyl)butanediamide

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)

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.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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).

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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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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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).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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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。