WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 555649
CAS#: 1130067-34-3
Description: CAY10594 is a potent phospholipase D2 inhibitor. CAY10594 ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3β/JNK axis. CAY10594 administration markedly blocked the acute liver injury in a dose-dependent manner, showing almost complete inhibition with 8 mg/kg of CAY10594. 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.
MedKoo Cat#: 555649
Name: CAY10594
CAS#: 1130067-34-3
Chemical Formula: C26H28N4O2
Exact Mass: 428.2212
Molecular Weight: 428.536
Elemental Analysis: C, 72.87; H, 6.59; N, 13.07; O, 7.47
Synonym: CAY10594; CAY-10594; CAY 10594;
IUPAC/Chemical Name: N-[2-(4-oxo-1-phenyl-1,3,8-triazaspiro[4,5]dec-8-yl)ethyl]-2-naphthalenecarboxamide
InChi Key: FAIFAFUXFFWVNQ-UHFFFAOYSA-N
InChi Code: InChI=1S/C26H28N4O2/c31-24(22-11-10-20-6-4-5-7-21(20)18-22)27-14-17-29-15-12-26(13-16-29)25(32)28-19-30(26)23-8-2-1-3-9-23/h1-11,18H,12-17,19H2,(H,27,31)(H,28,32)
SMILES Code: O=C(C1=CC=C2C=CC=CC2=C1)NCCN(CC3)CCC3(N(C4=CC=CC=C4)CN5)C5=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >3 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | PLD2 inhibitor |
| In vitro activity: | The current study investigated the mode of action of this compound on P2X7 activation. Measurements of ATP-induced ethidium(+) uptake revealed that CAY10593 impaired P2X7-induced pore formation in human RPMI 8226 B cells, P2X7-transfected HEK-293 cells and peripheral blood mononuclear cells. Concentration response curves demonstrated that CAY10593 impaired P2X7-induced pore formation in RPMI 8226 cells more potently than the PLD2 antagonist CAY10594 and the non-specific PLD antagonist halopemide. Electrophysiology measurements demonstrated that CAY10593 also inhibited P2X7-induced inward currents. Notably, RT-PCR demonstrated that PLD1 was absent in RPMI 8226 cells, while choline-Cl medium or 1-butanol, which block PLD stimulation and signalling respectively did not impair P2X7 activation in these cells. This data indicates that CAY10593 impairs human P2X7 independently of PLD1 stimulation and highlights the importance of ensuring that compounds used in signalling studies downstream of P2X7 activation do not affect the receptor itself. Reference: Pupovac A, Stokes L, Sluyter R. CAY10593 inhibits the human P2X7 receptor independently of phospholipase D1 stimulation. Purinergic Signal. 2013 Dec;9(4):609-19. doi: 10.1007/s11302-013-9371-6. Epub 2013 Jun 21. PMID: 23793974; PMCID: PMC3889394. |
| In vivo activity: | 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. Taken together, these results indicate that PLD2 is involved in the intrinsic response pathway of hepatocytes driving the pathogenesis of APAP-induced acute liver injury, and PLD2 may therefore represent an important therapeutic target for patients with drug-induced liver injury. Reference: Lee SK, Bae GH, Kim YS, Kim HS, Lee M, Ghim J, Zabel BA, Ryu SH, Bae YS. A phospholipase D2 inhibitor, CAY10594, ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3β/JNK axis. Sci Rep. 2019 May 10;9(1):7242. doi: 10.1038/s41598-019-43673-x. PMID: 31076618; PMCID: PMC6510900. |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 20.0 | 46.67 | |
| DMF | 20.0 | 46.67 | |
| DMSO:PBS(pH7.2) (1:1) | 0.5 | 1.17 |
The following data is based on the product molecular weight 428.536 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | Pupovac A, Stokes L, Sluyter R. CAY10593 inhibits the human P2X7 receptor independently of phospholipase D1 stimulation. Purinergic Signal. 2013 Dec;9(4):609-19. doi: 10.1007/s11302-013-9371-6. Epub 2013 Jun 21. PMID: 23793974; PMCID: PMC3889394. |
| In vitro protocol: | Pupovac A, Stokes L, Sluyter R. CAY10593 inhibits the human P2X7 receptor independently of phospholipase D1 stimulation. Purinergic Signal. 2013 Dec;9(4):609-19. doi: 10.1007/s11302-013-9371-6. Epub 2013 Jun 21. PMID: 23793974; PMCID: PMC3889394. |
| In vivo protocol: | Lee SK, Bae GH, Kim YS, Kim HS, Lee M, Ghim J, Zabel BA, Ryu SH, Bae YS. A phospholipase D2 inhibitor, CAY10594, ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3β/JNK axis. Sci Rep. 2019 May 10;9(1):7242. doi: 10.1038/s41598-019-43673-x. PMID: 31076618; PMCID: PMC6510900. |
1: Lingelem ABD, Kavaliauskiene S, Halsne R, Klokk TI, Surma MA, Klose C, Skotland T, Sandvig K. Diacylglycerol kinase and phospholipase D inhibitors alter the cellular lipidome and endosomal sorting towards the Golgi apparatus. Cell Mol Life Sci. 2021 Feb;78(3):985-1009. doi: 10.1007/s00018-020-03551-6. Epub 2020 May 23. PMID: 32447426; PMCID: PMC7897626.
2: Lee SK, Bae GH, Kim YS, Kim HS, Lee M, Ghim J, Zabel BA, Ryu SH, Bae YS. A phospholipase D2 inhibitor, CAY10594, ameliorates acetaminophen-induced acute liver injury by regulating the phosphorylated-GSK-3β/JNK axis. Sci Rep. 2019 May 10;9(1):7242. doi: 10.1038/s41598-019-43673-x. PMID: 31076618; PMCID: PMC6510900.
3: Zhou G, Yu L, Yang W, Wu W, Fang L, Liu Z. Blockade of PLD2 Ameliorates Intestinal Mucosal Inflammation of Inflammatory Bowel Disease. Mediators Inflamm. 2016;2016:2543070. doi: 10.1155/2016/2543070. Epub 2016 Sep 18. PMID: 27721573; PMCID: PMC5046040.
4: Choudhary V, Olala LO, Qin H, Helwa I, Pan ZQ, Tsai YY, Frohman MA, Kaddour- Djebbar I, Bollag WB. Aquaporin-3 re-expression induces differentiation in a phospholipase D2-dependent manner in aquaporin-3-knockout mouse keratinocytes. J Invest Dermatol. 2015 Feb;135(2):499-507. doi: 10.1038/jid.2014.412. Epub 2014 Sep 18. PMID: 25233074; PMCID: PMC7278525.
5: Hong-Brown LQ, Brown CR, Navaratnarajah M, Lang CH. Activation of AMPK/TSC2/PLD by alcohol regulates mTORC1 and mTORC2 assembly in C2C12 myocytes. Alcohol Clin Exp Res. 2013 Nov;37(11):1849-61. doi: 10.1111/acer.12174. Epub 2013 Jul 29. PMID: 23895284; PMCID: PMC3812405.
6: Pupovac A, Stokes L, Sluyter R. CAY10593 inhibits the human P2X7 receptor independently of phospholipase D1 stimulation. Purinergic Signal. 2013 Dec;9(4):609-19. doi: 10.1007/s11302-013-9371-6. Epub 2013 Jun 21. PMID: 23793974; PMCID: PMC3889394.
7: Roy A, Derakhshan F, Wilson RJ. Stress peptide PACAP engages multiple signaling pathways within the carotid body to initiate excitatory responses in respiratory and sympathetic chemosensory afferents. Am J Physiol Regul Integr Comp Physiol. 2013 Jun 15;304(12):R1070-84. doi: 10.1152/ajpregu.00465.2012. Epub 2013 Apr 17. PMID: 23594614.
