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CAY10594

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Chemical Structure| 1130067-34-3 同义名 : -
CAS号 : 1130067-34-3
货号 : A382489
分子式 : C26H28N4O2
纯度 : 98+%
分子量 : 428.526
MDL号 : MFCD18382100
存储条件:

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月

溶解度 :

DMSO: 10 mg/mL(23.34 mM),配合低频超声,并水浴加热至45℃助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO

动物实验配方:
生物活性
描述 Phospholipases (PLC, PLD and PLA) are essential mediators of intracellular and intercellular signalling. They can function as phospholipid-hydrolysing enzymes that can generate many bioactive lipid mediators, such as diacylglycerol, phosphatidic acid, lysophosphatidic acid and arachidonic acid. Lipid mediators generated by phospholipases regulate multiple cellular processes that can promote tumorigenesis, including proliferation, migration, invasion and angiogenesis[2]. CAY10594 is a potent phospholipase D2(PLD2) inhibitor. CAY10594 ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3β/JNK axis. CAY10594 administration markedly blocked the acute liver injury in a dose-dependent manner, showing almost complete inhibition with 8 mg/kg of CAY10594. During the pathological progress of acute liver injury, GSH levels are decreased, and this is significantly recovered upon the administration of CAY10594 at 6 hours post APAP challenge. GSK-3β (Serine 9)/JNK phosphorylation is mainly involved in APAP-induced liver injury. CAY10594 administration strongly blocked GSK-3β (Serine 9)/JNK phosphorylation in the APAP-induced acute liver injury model[3]. Consistently, sustained JNK activation in the cytosol and mitochondria from hepatocytes were also decreased in CAY10594-treated mice. Many types of immune cells are also implicated in APAP-induced liver injury. However, neutrophil and monocyte populations were not different between vehicle- and CAY10594-administered mice which are challenged with APAP. Therapeutic administration of CAY10594 also significantly attenuated liver damage caused by the APAP challenge, eliciting an enhanced survival rate. Mice were fasted for 16 hours before APAP injection. APAP (500 mg/kg) was administered with oral gavage in mice[4]. CAY10594 was dissolved in 1% DMSO and intraperitoneally administered to mice 30 minutes prior to APAP injection for examining protective effects or after 3 hours from APAP challenge for investigating therapeutic effects of CAY10594[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.33mL

0.47mL

0.23mL

11.67mL

2.33mL

1.17mL

23.34mL

4.67mL

2.33mL

参考文献

[1]Scott SA, Selvy PE, Buck JR, Cho HP, Criswell TL, Thomas AL, Armstrong MD, Arteaga CL, Lindsley CW, Brown HA. Design of isoform-selective phospholipase D inhibitors that modulate cancer cell invasiveness. Nat Chem Biol. 2009 Feb;5(2):108-17. doi: 10.1038/nchembio.140. Epub 2009 Jan 11. PMID: 19136975; PMCID: PMC3798018.

[2]Jong Bae Park,et al. Phospholipase signalling networks in cancer. Nat Rev Cancer.2012 Nov;12(11):782-92.

[3]Lee SK, Bae GH, Kim YS,et al.A phospholipase D2 inhibitor, CAY10594, ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3β/JNK axis.Sci Rep. 2019 May 10;9(1):7242.

[4]Pupovac A , Stokes L , Sluyter R . CAY10593 inhibits the human P2X7 receptor independently of phospholipase D1 stimulation[J]. Purinergic Signalling, 2013, 9(4):609-619.

[5]Zhang Y, Li Y, Liu P, et al. Phosphatase Shp2 regulates biogenesis of small extracellular vesicles by dephosphorylating Syntenin. Journal of extracellular vesicles. 2021, 10(5): e12078.