TAPI-1
(Synonyms: TAPI) 目录号 : GC12344
TAPI-1是一种TACE（肿瘤坏死因子-α转化酶）抑制剂，通过抑制TACE的蛋白水解酶活性，阻断其介导的细胞膜蛋白（两性调节蛋白（AREG））的胞外域脱落过程。
Cas No.:163847-77-6
Sample solution is provided at 25 µL, 10mM.
TAPI-1 is a TACE (tumor necrosis factor-α converting enzyme) inhibitor that blocks the shedding of the extracellular domain of cell membrane proteins (amphiregulin (AREG)) mediated by TACE by inhibiting its proteolytic activity[1, 2]. TAPI-1 is also a metalloproteinase (MMP) inhibitor[3]. TAPI-1 can reduce cellular oxidative stress and the production of inflammatory factors[4].
In vitro, TAPI-1 (0-20µM) treatment of TE-1 and Eca109 cells for 24h inhibited cell viability, migration, and invasion in a dose-dependent manner, and promoted cisplatin-induced apoptosis[5]. TAPI-1 (20µM) treatment of A549 cells for 24h reduced cell proliferation and inhibited EGFR and Notch1 mRNA expression[6]. TAPI-1 (5, 10µM) treatment of NCI-H292 cells for 6 and 24h blocked the shedding of amphiregulin (AREG) from the cell membrane stimulated by diacetyl[7].
In vivo, TAPI-1 (10mg/kg) administered by intraperitoneal injection to mice with Staphylococcus aureus-induced arthritis significantly reduced paw swelling and decreased the concentrations of superoxide, nitric oxide, and hydrogen peroxide in joint tissues[8].
References:
[1] Slack B E, Ma L K, Seah C C. Constitutive shedding of the amyloid precursor protein ectodomain is up-regulated by tumour necrosis factor-α converting enzyme[J]. Biochemical Journal, 2001, 357(3): 787-794.
[2] Liu C, Xu P, Lamouille S, et al. TACE-mediated ectodomain shedding of the type I TGF-β receptor downregulates TGF-β signaling[J]. Molecular cell, 2009, 35(1): 26-36.
[3] Koon H W, Zhao D, Na X, et al. Metalloproteinases and transforming growth factor-α mediate substance P-induced mitogen-activated protein kinase activation and proliferation in human colonocytes[J]. Journal of Biological Chemistry, 2004, 279(44): 45519-45527.
[4] Bae E H, Kim I J, Choi H S, et al. Tumor necrosis factor α-converting enzyme inhibitor attenuates lipopolysaccharide-induced reactive oxygen species and mitogen-activated protein kinase expression in human renal proximal tubule epithelial cells[J]. The Korean Journal of Physiology & Pharmacology, 2018, 22(2): 135-143.
[5] Gao L, Li L, Zhang D, et al. TAPI-1 exhibits Anti-tumor efficacy in human esophageal squamous cell carcinoma cells via suppression of NF-κB signaling pathway[J]. Digestive Diseases and Sciences, 2024, 69(1): 81-94.
[6] Pancewicz J, Golec P. The effect of TAPI-1 treatment in non-small cell lung cancer cells[J].
[7] Kelly F L, Sun J, Fischer B M, et al. Diacetyl induces amphiregulin shedding in pulmonary epithelial cells and in experimental bronchiolitis obliterans[J]. American journal of respiratory cell and molecular biology, 2014, 51(4): 568-574.
[8] Sultana S, Bishayi B. Potential anti-arthritic and anti-inflammatory effects of TNF-α processing inhibitor-1 (TAPI-1): A new approach to the treatment of S. aureus arthritis[J]. Immunobiology, 2020, 225(2): 151887.
TAPI-1是一种TACE（肿瘤坏死因子-α转化酶）抑制剂，通过抑制TACE的蛋白水解酶活性，阻断其介导的细胞膜蛋白（两性调节蛋白（AREG））的胞外域脱落过程[1, 2]。TAPI-1是一种金属蛋白酶（MMP）抑制剂[3]。TAPI-1能够减轻细胞氧化应激和炎症因子的产生[4]。
在体外，TAPI-1（0-20µM）处理TE-1、Eca109细胞24h，均以剂量依赖性方式抑制了细胞活力，抑制了细胞迁移和侵袭，促进了顺铂诱导的细胞凋亡[5]。TAPI-1（20µM）处理A549细胞24h，减少了细胞的增殖，抑制了EGFR和Notch1的mRNA表达[6]。TAPI-1（5, 10µM）处理NCI-H292细胞6h和24h，阻断了Diacetyl刺激下两性调节蛋白（AREG）从细胞膜上被切割释放的过程[7]。
在体内，TAPI-1（10mg/kg）通过腹腔注射治疗金黄色葡萄球菌感染的关节炎小鼠，显著减轻了小鼠的爪部肿胀，降低了关节组织中的超氧化物、一氧化氮和过氧化氢浓度[8]。
| Cell experiment [1]: | |
Cell lines | TE-1、Eca109 cells |
Preparation Method | TE-1 and Eca109 cells were exposed tovarying doses of TAPI-1 (0, 1.25, 2.5, 5, 10, and 20μM) for 24h, following which, cell viability was determined using CCK-8 assay. |
Reaction Conditions | 0, 1.25, 2.5, 5, 10, 20μM; 24h |
Applications | Following exposure of TAPI-1, TE-1, and Eca109 cell viability was inhibited in a dose dependent manner. |
| Animal experiment [2]: | |
Animal models | Adult Swiss albino male mice |
Preparation Method | TAPI-1 was diluted in 5% DMSO in sterile saline solution. The final concentration used was 10mg/kg of body weight. The first dose of TAPI-1 was administered intraperitoneally into each mouse 24h after S.aureus infection and repeated at day 4, day 7, day 10 and day 13 post infection. Control mice received a single dose of TAPI-1 two days prior to sacrifice. |
Dosage form | 10mg/kg; i.p. |
Applications | TAPI-1 administration significantly reduced paw swelling in mice with Staphylococcus aureus-induced arthritis. Following TAPI-1 treatment, the concentrations of superoxide, nitric oxide, and hydrogen peroxide were all reduced in the arthritic joints. |
References: | |
| Cas No. | 163847-77-6 | SDF | |
| 别名 | TAPI | ||
| 化学名 | N1-((R)-1-(((R)-1-((2-aminoethyl)amino)-1-oxopropan-2-yl)amino)-3-(naphthalen-2-yl)-1-oxopropan-2-yl)-N4-hydroxy-2-isobutylsuccinamide | ||
| Canonical SMILES | NCCNC([C@@H](C)NC([C@H](NC(C(CC(C)C)CC(NO)=O)=O)CC1=CC2=CC=CC=C2C=C1)=O)=O | ||
| 分子式 | C26H37N5O5 | 分子量 | 499.6 |
| 溶解度 | ≥ 24.98mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.0016 mL | 10.008 mL | 20.016 mL |
| 5 mM | 400.3 μL | 2.0016 mL | 4.0032 mL |
| 10 mM | 200.2 μL | 1.0008 mL | 2.0016 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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2.
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Quality Control & SDS
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- Purity: >98.00%
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