Cl-Amidine (trifluoroacetate salt)
目录号 : GC11032
Cl-Amidine (trifluoroacetate salt) 是一种具有口服活性的肽基精氨酸脱氨酶 (PAD) 抑制剂，对于 PAD1、PAD3 和 PAD4 的 IC50 值分别为 0.8 μM, 6.2 μM 和 5.9 ⋼M。
Cas No.:1043444-18-3
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
|
Cell experiment: |
TK6 cells are a lymphoblastoid cell line derived from the spleen >30 years ago. HT29 cells are a colon cancer cell line, with mutant p53. TK6 lymphoblastoid cells and HT29 colon cancer cells are cultured with Cl-amidine in a dose-dependent manner (0, 5, 10, 15, 20, 25, 50 μg/mL) over 24 h. Apoptosis is assessed by annexin V/propidium iodide staining followed by flow cytometry[2]. |
|
Animal experiment: |
Mice[2]C57BL/6 mice (8-12 wk old) are fed a standard AIN 93M diet. For this DSS mouse model of colitis, mice receive water ad libitum or 2% DSS beginning at day 0 [for oral gavage/treatment experiment or day 7 [for intraperitoneal/prevention experiment. Initial experiments used injections of Cl-amidine (75 mg/kg-1/day-1 ip), beginning concomitantly with the initiation of 2% DSS in the drinking water. This dose is chosen based on results in a RA model that used 100 mg/kg-1/day-1 without overt side effects and without immunosuppressive outcomes. In DSS model, 50 mice in 4 groups are examined, and inflammation scores are recorded[2]. |
|
References: [1]. Yuan Luo, et al. Inhibitors and Inactivators of Protein Arginine Deiminase 4: Functional and Structural Characterization. Biochemistry. 2006 Oct 3; 45(39): 11727–11736. |
|
IC50: 5.9 μM
Cl-Amidine is a PAD4 deimination activity inhibitor.
Protein arginine deiminase 4 (PAD4) can catalyze the post-translational modification of arginine residues on histones to form citrulline, which can change gene expression. Thus, dysregulated PAD4 activity has been implicated in cancer and rheumatoid arthritis.
In vitro: Previous study found that Cl-amidine antagonized the PAD4-mediated enhancement of the the p300GBD-GRIP1 interaction dose-dependently, and it was noteworthy that Cl-amidine treatment had only a minimal reduction in the efficiency of the interaction in Cys645S-transfected cells, thereby suggesting that the inhibitory effect of Cl-amidine was not a nonspecific one but was targeted at the active PAD4 enzyme. These results demonstrated that Cl-amidine was significantly more potent than F-amidine, consistent with its improved in vitro potency [1].
In vivo: Animal study showed that Cl-amidine could improve survival in a mouse model of cecal ligation and puncture (CLP)-induced septic shock. Cl-amidine was proven to play protective roles by restoring innate immune cells in BM, decreasing BM and thymus atrophy, increasing blood monocytes and blood/liver bacteria clearance, and attenuating pro-inflammatory cytokine production in a murine lethal sepsis model [2].
Clinical trial: So far, no clinical study has been conducted.
References:
[1] Luo, Y. ,Arita, K.,Bhatia, M., et al. Inhibitors and inactivators of protein arginine deiminase 4: Functional and structural characterization. Biochemistry 45(39), 11727-11736 (2006).
[2] Zhao T, Pan B, Alam HB, Liu B, Bronson RT, Deng Q, Wu E, Li Y. Protective effect of Cl-amidine against CLP-induced lethal septic shock in mice. Sci Rep. 2016 Nov 7;6:36696.
IC50:5.9 μM
Cl-Amidine 是一种 PAD4 脱亚胺活性抑制剂。
蛋白质精氨酸脱亚胺酶 4 (PAD4) 可以催化组蛋白上精氨酸残基的翻译后修饰形成瓜氨酸，它可以改变基因表达。因此，失调的 PAD4 活性与癌症和类风湿性关节炎有关。
体外:先前的研究发现，氯脒拮抗 PAD4 介导的 p300GBD-GRIP1 相互作用的剂量依赖性增强，并且它值得注意的是，Cl-脒处理在 Cys645S 转染细胞中的相互作用效率只有极小的降低，从而表明 Cl-脒的抑制作用不是非特异性的，而是针对活性 PAD4 酶。这些结果表明 Cl-脒比 F-脒更有效，与其提高的体外效力一致 [1]。
体内:动物研究表明 Cl-脒可以提高小鼠的存活率盲肠结扎穿孔 (CLP) 诱导的感染性休克模型。事实证明，在小鼠致死性败血症模型中，氯脒通过恢复 BM 中的先天免疫细胞、减少 BM 和胸腺萎缩、增加血液单核细胞和血液/肝脏细菌清除率以及减弱促炎细胞因子的产生来发挥保护作用 [2]。
临床试验:目前尚未进行临床研究。
| Cas No. | 1043444-18-3 | SDF | |
| 化学名 | N-[(1S)-1-(aminocarbonyl)-4-[(2-chloro-1-iminoethyl)amino]butyl]-benzamide 2,2,2-trifluoroacetate | ||
| Canonical SMILES | O=C(N[C@@H](CCCNC(CCl)=N)C(N)=O)C1=CC=CC=C1.FC(F)(C(O)=O)F | ||
| 分子式 | C14H19ClN4O2 • CF3CO2H | 分子量 | 424.8 |
| 溶解度 | DMF: 14 mg/ml, DMSO: 100 mg/ml, water: 3 mg/ml | 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。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.354 mL | 11.7702 mL | 23.5405 mL |
| 5 mM | 0.4708 mL | 2.354 mL | 4.7081 mL |
| 10 mM | 0.2354 mL | 1.177 mL | 2.354 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % 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，
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 saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。