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CPYPP
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
CPYPP图片
包装与价格:
包装价格(元)
10mg电议
50mg电议

产品介绍
CPYPP 是一种 DOCK2-Rac1 相互作用抑制剂。

Cell lines

Spleen cells of BALB/c mice

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.

Reaction Conditions

100µM for 1 hour or 5 hours

Applications

CPYPP was nontoxic when applied to spleen cells at 100 µM .

Animal models

male C57BL/6J mice

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.

Dosage form

Intraperitoneal injection, 250 mg/kg

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.

产品描述

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.