PBP 10 (trifluoroacetate salt) is a cell-permeable formyl peptide receptor 2 (FPR2) antagonist[1-2]. PBP 10 (trifluoroacetate salt) exhibits multiple biological activities, including antibacterial, antiviral, and cancer-inhibitory effects[3-4].
In vitro, pretreatment of human keratinocytes (HaCaT) with PBP 10 (trifluoroacetate salt) (2-10μg/mL) for 20 minutes significantly suppresses the release of pro-inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS), and interleukin-8 (IL-8) induced by stimulation with lipopolysaccharide (LPS; 1μg/mL) or lipoteichoic acid (LTA; 1μg/mL), while also reversing inflammation-related nanomechanical changes, such as the reduction in cell stiffness caused by LPS[5]. Pretreatment of RT4 Schwann cells with PBP 10 (trifluoroacetate salt) (1 μM) for 20 minutes, followed by stimulation with fMLF (10nM–100nM) for 6 hours, significantly inhibits fMLF-induced upregulation of Fpr2 protein expression and the decrease in p-NFκB levels, while also reversing changes in the expression of CCR2, CXCR4, and PKCβ[6].
References:
[1] Forsman H, Andréasson E, Karlsson J, et al. Structural characterization and inhibitory profile of formyl peptide receptor 2 selective peptides descending from a PIP2-binding domain of gelsolin. J Immunol. 2012 Jul 15;189(2):629-37.
[2] Holdfeldt A, Winther M, Gabl M, et al. Data on human neutrophil activation induced by pepducins with amino acid sequences derived from β2AR and CXCR4. Data Brief. 2016 Jun 1;8:411-4.
[3] Courtin N, Fotso AF, Fautrad P, et al. Antiviral activity of formyl peptide receptor 2 antagonists against influenza viruses. Antiviral Res. 2017 Jul;143:252-261.
[4] Jia G, Wang X, Wu W, et al. LXA4 enhances prostate cancer progression by facilitating M2 macrophage polarization via inhibition of METTL3. Int Immunopharmacol. 2022 Jun;107:108586.
[5] Korimová A, Dubový P. N-Formylated Peptide Induces Increased Expression of Both Formyl Peptide Receptor 2 (Fpr2) and Toll-Like Receptor 9 (TLR9) in Schwannoma Cells-An In Vitro Model for Early Inflammatory Profiling of Schwann Cells. Cells. 2020 Dec 11;9(12):2661.
[6] Xu J, Su Z, Cheng X, et al. High PPT1 expression predicts poor clinical outcome and PPT1 inhibitor DC661 enhances sorafenib sensitivity in hepatocellular carcinoma. Cancer Cell Int. 2022 Mar 11;22(1):115.
PBP 10 (trifluoroacetate salt)是一种具有细胞通透性的甲酰肽受体2（FPR2）拮抗剂[1-2]。PBP 10 (trifluoroacetate salt)具有多种生物学活性，包括抗菌、抗病毒和抑制癌症[3-4]。
在体外，PBP 10 (trifluoroacetate salt)（2-10μg/mL）预处理人皮肤角质形成细胞（HaCaT）孵育20分钟，可显著抑制由脂多糖（LPS；1μg/mL）或脂磷壁酸（LTA；1μg/mL）刺激所诱导的一氧化氮（NO）、活性氧（ROS）及白细胞介素-8（IL-8）等促炎介质的释放，同时逆转LPS引起的细胞刚度降低等炎症反应相关的纳米力学特性改变[5]。PBP 10 (trifluoroacetate salt)（1μM）预处理RT4 Schwann细胞20分钟，随后以fMLF（10nM–100nM）刺激6小时，显著抑制fMLF诱导的Fpr2蛋白表达上调和p-NFκB水平降低，同时逆转CCR2、CXCR4及PKCβ的表达变化[6]。