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CAY10594

Catalog No.GC18691

CAY10594 is an effective inhibitor of phospholipase D2 (PLD2) (IC50 140 nm in vitro and 110 nm in cells).

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CAY10594 Chemical Structure

Cas No.: 1130067-34-3

Size Price Stock Qty
1mg
$35.00
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5mg
$180.00
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10mg
$275.00
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25mg
$522.00
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

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Protocol

Cell experiment [1]:

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 experiment [2]:

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.

Background

CAY10594 is an effective inhibitor of phospholipase D2 (PLD2) (IC50 140 nm in vitro and 110 nm in cells). Cay10594 highly inhibits the invasive migration of breast cancer cells in vitro and regulates the phosphorylation of GSK-3 β/ JNK axis ameliorates paracetamol induced acute liver injury.

CAY10594 significantly improved intestinal mucosal inflammation, which was characterized by higher survival rate, slight decrease in body weight, less or no bloody stool and lower pathological score level,compared with the control group. RNA was extracted from colon tissue to detect the expression of cytokines, as well as proinflammatory cytokines, such as TNF- α¡¢ IL-6, IL-23 and IL-1 β It was found that PLD2 was significantly decreased after blocking in DSS induced colitis, while anti-inflammatory cytokines were significantly increased after inhibiting PLD2. In addition, fresh colon samples were also obtained and cultured in vitro for 24 hours; The supernatant was collected to detect cytokines by ELISA. Proinflammatory cytokines (e.g., IL-17A, TNF- α and IL-1 β) [1] While anti-inflammatory cytokines (for example, IL-10 was found to increase after PLD2 blockade), indicating that PLD2 blockade can improve intestinal mucosal inflammation [2].

CAY10594 induced a strong therapeutic effect in APAP challenged mice. The results show that PLD2 plays an important role in mediating APAP induced liver injury [3]. Because PLD2 has basic activity, the administration of cay10594 will block the production of PLD2 enzyme active product PA in an experimental acute liver injury model. Therefore, it is reasonable to assume that the protective and therapeutic effects of cay10594 in the acute liver injury model will be mediated by blocking the production of PA. Cay10594 may regulate early liver pathology to prevent APAP induced liver injury by rapidly restoring GSH levels without affecting antioxidant gene expression [4].

References:
[1] Lee S K, Kim S D, Kook M, et al. Phospholipase D2 drives mortality in sepsis by inhibiting neutrophil extracellular trap formation and down-regulating CXCR2[J]. Journal of Experimental Medicine, 2015, 212(9): 1381-1390.
[2] Zhou G, Yu L, Yang W, et al. Blockade of PLD2 ameliorates intestinal mucosal inflammation of inflammatory bowel disease[J]. Mediators of inflammation, 2016, 2016.
[3] Mitchell J R, Jollow D J, Potter W Z, et al. Acetaminophen-induced hepatic necrosis. I. Role of drug metabolism[J]. Journal of Pharmacology and Experimental Therapeutics, 1973, 187(1): 185-194.
[4] 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.

Chemical Properties

Cas No. 1130067-34-3 SDF
Chemical Name N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)ethyl]-2-naphthalenecarboxamide
Canonical SMILES O=C(NCCN1CCC2(C(NCN2C3=CC=CC=C3)=O)CC1)C4=CC(C=CC=C5)=C5C=C4
Formula C26H28N4O2 M.Wt 428.5
Solubility DMF: 20 mg/ml,DMSO: 20 mg/ml,DMSO:PBS(pH7.2) (1:1): 0.5 mg/ml Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

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1 mg 5 mg 10 mg
1 mM 2.3337 mL 11.6686 mL 23.3372 mL
5 mM 0.4667 mL 2.3337 mL 4.6674 mL
10 mM 0.2334 mL 1.1669 mL 2.3337 mL
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Average Rating: 5 ★★★★★ (Based on Reviews and 7 reference(s) in Google Scholar.)

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