| Description | CAY10594 is a potent phospholipase D2(PLD2) inhibitor. CAY10594 ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3β/JNK axis. |
| In vivo | 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. 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[1]. |
| Animal experiments | Mice were fasted for 16?hours before APAP injection. APAP (500?mg/kg) was administered with oral gavage in mice. CAY10594 (N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)ethyl]-2-naphthalene carboxamide)23 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[1]. |
| molecular weight | 428.53 |
| Molecular formula | C26H28N4O2 |
| CAS | 1130067-34-3 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 20mg/ml(46.7mM) |
| References | 1. 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[J].Sci Rep. 2019 May 10;9(1):7242. 2. 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. 3. Zhang Y, Li Y, Liu P, et al. Phosphatase Shp2 regulates biogenesis of small extracellular vesicles by dephosphorylating Syntenin[J]. Journal of extracellular vesicles. 2021, 10(5): e12078. |
| Citations | 1. Zhang Y, Li Y, Liu P, et al. Phosphatase Shp2 regulates biogenesis of small extracellular vesicles by dephosphorylating Syntenin. Journal of extracellular vesicles. 2021 Mar;10(5):e12078. doi: 10.1002/jev2.12078. Epub 2021 Mar 10. 2. Liu Z, Nan Y, Luo Q, et al. DLGAP1-AS2-Mediated Phosphatidic Acid Synthesis Activates YAP Signaling and Confers Chemoresistance in Squamous Cell Carcinoma. Cancer Research. 2022 |