CPYPP
目录号 : GC50065
CPYPP 以可逆方式与 DOCK2 DHR-2 结构域 (DOCK2DHR-2) 结合并抑制其催化活性。
Cas No.:310460-39-0
Sample solution is provided at 25 µL, 10mM.
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CPYPP bound to DOCK2 DHR-2 domain (DOCK2DHR-2) in a reversible manner and inhibited its catalytic activity[1].
CPYPP inhibited the guanine nucleotide exchange factor (GEF) activity of DOCK2DHR-2 for Rac1 in a dose-dependent manner, with a half-maximal inhibitory concentration (IC50) of 22.8 ± 2.4 μM. This inhibitory activity was independent on length of preincubation time, ranging from 2 min to 30 min. In addition, CPYPP was nontoxic when applied to spleen cells or thymoma cells (BW5147α-β-) at 100 μM for 3 hr or 3 days, respectively [1]. Pre-treatment of human neutrophils with CPYPP, a small molecule inhibitor of the DHR-2 domain of DOCK proteins and thus of the Rac GEF activity of human DOCK2 and DOCK5, significantly impaired neutrophil chemotaxis and ROS production [2].
CPYPP effectively decreased the secretion and gene expression of TNF-α, IL-1β and IL-6 in the lungs, suggested effects of DOCK2 on endotoxemia-induced inflammatory responses in mice. CPYPP remarkably inhibited the infiltration of total cells, macrophages and neutrophils into the bronchoalveolar lavage fluid [3]. A reseach found out that a joint usage of both CPYPP and C25-140 revealed a better consequence compared to monotherapy against hepatic I/R injury [4].
References:
[1]. Nishikimi?A, Uruno?T, Duan?X, Cao?Q, Okamura?Y, Saitoh?T, et al.?Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK2. Chem Biol?2012;19:488-97.
[2]. Moens, L., Gouwy, M., Bosch, B. et al. 2019. Human DOCK2 deficiency: report of a novel mutation and evidence for neutrophil dysfunction. J. Clin. Immunol. 39:298.
[3]. Xu, X., Su, Y., Wu, K., Pan, F. & Wang, A. DOCK2 contributes to endotoxemia-induced acute lung injury in mice by activating proinflammatory macrophages. Biochem. Pharmacol. 181, 114399 (2021).
[4]. Zuotian Huang, Junliang Pua, Yunhai Luo, et al. FAM49B, restrained by miR-22, relieved hepatic ischemia/reperfusion injury by inhibiting TRAF6/IKK signaling pathway in a Rac1-dependent manner. Molecular Immunology.143, 2022, 135-146.
CPYPP 以可逆方式与 DOCK2 DHR-2 结构域 (DOCK2DHR-2) 结合并抑制其催化活性[1]。
CPYPP 以剂量依赖性方式抑制 DOCK2DHR-2 鸟嘌呤核苷酸交换因子 (GEF) 对 Rac1 的活性，半数最大抑制浓度 (IC50) 为 22.8 ± 2.4 μM .这种抑制活性与预孵育时间的长度无关，范围从 2 分钟到 30 分钟。此外，CPYPP 在以 100 μM 分别作用于脾细胞或胸腺瘤细胞 (BW5147α-β-) 3 小时或 3 天时是无毒的[1]。用 CPYPP 预处理人中性粒细胞，CPYPP 是一种小分子抑制剂，可抑制 DOCK 蛋白的 DHR-2 结构域，从而抑制人 DOCK2 和 DOCK5 的 Rac GEF 活性，显着损害中性粒细胞趋化性和 ROS 产生[2].
CPYPP 有效降低肺部 TNF-α、IL-1β 和 IL-6 的分泌和基因表达，表明 DOCK2 对小鼠内毒素血症诱导的炎症反应有影响。 CPYPP显着抑制总细胞、巨噬细胞和中性粒细胞向支气管肺泡灌洗液中的浸润[3]。一项研究发现，与单一疗法相比，CPYPP 和 C25-140 联合使用对肝 I/R 损伤具有更好的疗效[4]。
| Cell experiment [1]: | |
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Cell lines |
Spleen cells of BALB/c mice |
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Preparation Method |
Spleen cells of BALB/c mice (1 × 107/ml) were incubated in RPMI1640 medium supplemented with 0.5% BSA or 10% FCS in the presence or absence of 100 µM CPYPP. 1 or 5 hr of incubation at 37°C. |
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Reaction Conditions |
100µM for 1 hour or 5 hours |
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Applications |
CPYPP was nontoxic when applied to spleen cells at 100 µM . |
| Animal experiment [2]: | |
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Animal models |
male C57BL/6J mice |
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Preparation Method |
Mice were randomized into four groups (n = 6): the saline + vehicle group, LPS + vehicle group, saline + CPYPP group, and LPS + CPYPP group. ALI was induced by intraperitoneal (i.p.) injection of LPS (10 mg/kg) body weight; The mice in the LPS + vehicle and LPS + CPYPP groups received CPYPP (250 mg/kg) or an equivalent volume of vehicle via i.p. injection 10 min after LPS administration. The mice in the saline + vehicle and saline + CPYPP groups received CPYPP (250 mg/kg) or an equivalent volume of vehicle via i.p. injection 10 min after saline administration. |
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Dosage form |
Intraperitoneal injection, 250 mg/kg |
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Applications |
CPYPP-treated mice had decreased lung injury scores compared with vehicle-treated mice. Furthermore, CPYPP-treated mice exhibited significantly decreased MPO activity and W/D ratios, which indicated decreased pulmonary edema. |
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References: [1]: Nishikimi?A, Uruno?T, Duan?X, Cao?Q, Okamura?Y, Saitoh?T, et al.?Blockade of inflammatory responses by a small-molecule inhibitor of the Rac activator DOCK2. Chem Biol?2012;19:488-97. |
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| Cas No. | 310460-39-0 | SDF | |
| Canonical SMILES | O=C(N(C3=CC=CC=C3)NC2=O)/C2=C\C=C\C1=C(Cl)C=CC=C1 | ||
| 分子式 | C18H13ClN2O2 | 分子量 | 324.76 |
| 溶解度 | DMSO: 50 mM | 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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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0792 mL | 15.396 mL | 30.792 mL |
| 5 mM | 0.6158 mL | 3.0792 mL | 6.1584 mL |
| 10 mM | 0.3079 mL | 1.5396 mL | 3.0792 mL |
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| 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 |
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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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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。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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