CAY10650 is a highly potent cytosolic phospholipase A2α (cPLA2α) inhibitor with an IC50 value of 12nM[1]. cPLA2α is a crucial enzyme involved in the hydrolysis of phospholipids to release arachidonic acid and is essential for mediating inflammatory responses and cellular signaling pathways[2][3]. CAY10650 is typically used for studying inflammation and cellular signaling pathways related to phospholipase A2[4][5].
In vitro, CAY10650 (12nM; 30min) inhibit the phosphorylation of cPLA2α, and reduced lipid body formation and PGE2 secretion in human neutrophils stimulated with Cr-LAAO[1].
In vivo, CAY10650 (50μg in 5μl eye-drop) attenuated corneal inflammation and decreased neutrophil infiltration when applied topically three times daily for 6 days and then daily from days 7 to 15 post-infection in Chinese hamsters infected with Acanthamoeba castellanii in the eyes[6]. CAY10650 (20μg/ear/day) reduced ear thickness, epidermal thickness, and inflammatory infiltrates in an IMQ-induced psoriasis mouse model when applied topically for 5 days[7].
References:
[1] Paloschi MV, Lopes JA, Boeno CN, et al. Cytosolic phospholipase A2-α participates in lipid body formation and PGE2 release in human neutrophils stimulated with an L-amino acid oxidase from Calloselasma rhodostoma venom. Sci Rep. 2020;10(1):10976.
[2] Murakami M, Kudo I. Phospholipase A2. J Biochem. 2002;131(3):285-292.
[3] Yang D, Ji HF, Zhang XM, et al. Protective effect of cytosolic phospholipase A2 inhibition against inflammation and degeneration by promoting regulatory T cells in rats with experimental autoimmune encephalomyelitis. Mediators Inflamm. 2014;2014:890139.
[4] Lin CY, Xu WB, Li BZ, Shu MA, Zhang YM. Identification and functional analysis of cytosolic phospholipase A2 (cPLA2) from the red swamp crayfish Procambarus clarkii: The first evidence of cPLA2 involved in immunity in invertebrates. Fish Shellfish Immunol. 2023;140:108944.
[5] Wu CZ, Li X, Hong L, et al. NOX4/Src regulates ANP secretion through activating ERK1/2 and Akt/GATA4 signaling in beating rat hypoxic atria. Korean J Physiol Pharmacol. 2021;25(2):159-166.
[6] Tripathi T, Abdi M, Alizadeh H. Role of phospholipase A₂ (PLA₂) inhibitors in attenuating apoptosis of the corneal epithelial cells and mitigation of Acanthamoeba keratitis. Exp Eye Res. 2013;113:182-191.
[7] Shao S, Chen J, Swindell WR, et al. Phospholipase A2 enzymes represent a shared pathogenic pathway in psoriasis and pityriasis rubra pilaris. JCI Insight. 2021;6(20):e151911.
CAY10650是一种高效的细胞质磷脂酶A2α（cPLA2α）抑制剂，IC50值为12nM[1]。cPLA2α是一种关键酶，参与磷脂的水解以释放花生四烯酸，对于介导炎症反应和细胞信号传导通路至关重要[2][3]。CAY10650通常用于研究与磷脂酶A2相关的炎症和细胞信号传导通路研究[4][5]。
在体外实验中，CAY10650（12nM；30分钟）抑制了Cr-LAAO刺激的人类中性粒细胞中cPLA2α的磷酸化，并减少了脂滴形成和PGE2分泌[1]。
在体内实验中，CAY10650（50μg in 5μl眼药水）通过局部给药，每天三次，持续6天，然后从第7天到第15天每天一次，用于眼部感染棘阿米巴原虫的中国仓鼠，显著减轻了角膜炎症并减少了中性粒细胞的浸润[6]。CAY10650（20μg/耳/天）在IMQ诱导的银屑病小鼠模型中，通过局部给药，连续5天，显著减少了耳部厚度、表皮厚度和炎症细胞浸润[7]。