CAY10594

Cell lines

Human RPMI 8226 multiple myeloma B cells and human A431 skin epithelial carcinoma cells

Preparation Method

Human RPMI 8226 multiple myeloma B cells and human A431 skin epithelial carcinoma cells were maintained in complete RPMI-1640 medium at 37 °C and 95 % air/5 % CO2. HEK-293 cells were maintained in complete DMEM/F12 medium. Cells in NaCl medium were pre-incubated at 37 °C for 15 min in the presence of DMSO, or 10 µM CAY10593, CAY10594 or halopemide.

Reaction Conditions

10 µM for 500 seconds

Applications

The PLD1 antagonist CAY10593 and to a lesser extent the PLD2 antagonist CAY10594 (both at 10 µM) significantly impaired ATP-induced CD23 shedding. The non-selective PLD antagonist and structural analogue of CAY10593, halopemide (10 µM) however had no significant effect on ATP-induced CD23 shedding. In the absence of ATP, no antagonist significantly altered cell-surface expression of CD23 compared to control-treated cells.

Animal models

C57BL/6 mice

Preparation Method

Mice were fasted for 16 hours before APAP injection. APAP (500 mg/kg) was administered with oral gavage in mice. 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.

Dosage form

4/8/mg/kg

Applications

Injection of APAP (500 mg/kg) caused marked liver injury, which was measured by hematoxylin and eosin staining of the livers. APAP-induced liver injury was almost completely blocked by the administration of a CAY10594 in a dose-dependent manner. APAP-induced hepatocyte death was measured by the TUNEL assay. Hepatocyte apoptosis was induced by APAP, which was also markedly decreased in CAY10594-administered mice compared with vehicle-treated mice. The protective effects of the CAY10594 against hepatocyte apoptosis were strongly induced at 4 or 8 mg/kg.

References:

[1]. 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.
[2]. Lee S K, Bae G H, Kim Y S, et al. A phospholipase D2 inhibitor, CAY10594, ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3β/JNK axis[J]. Scientific Reports, 2019, 9(1): 1-10.