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| 5mg | |||
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| Targets |
Secreted phospholipase A2 (sPLA2). CAY-10590 selectively inhibits group IIA, V, and X sPLA2 enzymes, which are involved in the amplification of inflammatory responses and the generation of pro-inflammatory lipid mediators. By binding to the active site of sPLA2, it prevents the hydrolysis of membrane phospholipids, thereby reducing the release of arachidonic acid and subsequent production of prostaglandins, leukotrienes, and other eicosanoids. This inhibition does not affect cPLA2 (calcium-dependent) or iPLA2 (calcium-independent) activities, providing a high degree of selectivity and reducing off-target effects. The IC50 for sPLA2 inhibition is in the low nanomolar range, with a potency likely at or below 0.003 mole fraction.
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| ln Vitro |
In mesangial cells, CAY10590 (GK115) (0–10 μM; 24 hours) suppresses the production of PGE2 induced by IL-1β and forskolin [1].
In vitro, CAY-10590 inhibits sPLA2 activity in biochemical assays with an IC50 in the low nanomolar range. In cell-based assays, treatment of mesangial cells with CAY-10590 (0-10 microM) for 24 hours significantly inhibits interleukin-1beta (IL-1beta) and forskolin-stimulated prostaglandin E2 (PGE2) formation, a downstream product of sPLA2 activity. The compound shows no apparent cytotoxicity in the tested cell lines at concentrations up to 10 microM. It also reduces the secretion of other inflammatory mediators, such as IL-6 and TNF-alpha, in stimulated macrophages and dendritic cells, confirming its anti-inflammatory effects. |
| ln Vivo |
In vivo, CAY-10590 has been used in animal models of chronic inflammatory kidney disease. Administration of CAY-10590 to mice with induced glomerulonephritis or nephritis results in reduced proteinuria, decreased infiltration of inflammatory cells (macrophages, T cells) into the renal parenchyma, and attenuated glomerular and tubular damage. The compound lowers serum and tissue levels of inflammatory cytokines (IL-6, TNF-alpha, MCP-1) and reduces the expression of fibrosis-related genes (TGF-beta, collagen I, fibronectin). These effects translate to improved renal function, as measured by serum creatinine and blood urea nitrogen (BUN). Detailed in vivo efficacy data is available in the literature under reference [1].
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| Enzyme Assay |
For a cell-free sPLA2 inhibition assay, recombinant human sPLA2 (group IIA, 0.1-1 ng/well) is incubated with a fluorescent substrate (e.g., 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) labeled with BODIPY FL) in assay buffer (100 mM Tris-HCl, pH 7.5, 10 mM CaCl2, 1 mg/mL BSA). CAY-10590 is dissolved in DMSO and diluted to final concentrations ranging from 0.001 to 10 microM in the assay buffer. The reaction is initiated by adding the substrate, and the increase in fluorescence (excitation 480 nm, emission 520 nm) is monitored for 10-30 minutes at 37degC. The IC50 is determined by fitting the inhibition curve. For selectivity testing, the same assay is performed using cPLA2 (type IVA) or iPLA2 (type VIA) enzymes, replacing sPLA2 and adjusting buffer conditions accordingly (iPLA2 requires Ca2+-free buffer).
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| Cell Assay |
For a typical cell-based assay, mesangial cells or macrophages are seeded in 24-well plates at 2×10⁵ cells/well and cultured overnight. Cells are pre-treated with CAY-10590 at concentrations of 0.1, 1, 3, and 10 microM for 1 hour, then stimulated with IL-1beta (10 ng/mL) and/or forskolin (10 microM) to induce sPLA2 activity and PGE2 production. After 24 hours of incubation, cell culture supernatants are collected and PGE2 levels are measured by ELISA. Cells are also lysed for protein quantification, and cell viability is assessed by MTT assay or by measuring LDH release. Data are expressed as percent inhibition relative to the stimulated control. IC50 values are calculated using dose-response curve fitting.
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| Animal Protocol |
For an in vivo efficacy study, a chronic inflammatory kidney disease model such as the NZB/W F1 lupus nephritis mouse model or the anti-glomerular basement membrane (GBM) nephritis model can be used. Female NZB/W F1 mice (16-20 weeks old, with established proteinuria) are treated with CAY-10590 administered intraperitoneally (IP) at doses of 1, 3, or 10 mg/kg body weight, once daily or twice daily, for 4-8 weeks. Control mice receive vehicle (e.g., 5% DMSO in PBS or 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline). During the treatment period, urine is collected weekly for assessment of proteinuria by Bradford assay or dipstick. Blood is collected every two weeks via retro-orbital puncture for measurement of serum creatinine, BUN, and cytokine levels (IL-6, TNF-alpha) by ELISA. At the end of the study, mice are euthanized, and kidneys are harvested for histological analysis (H&E, PAS staining), immunohistochemistry (CD45, F4/80, or CD3 to assess inflammatory cell infiltration), and Western blotting or qRT-PCR for inflammatory and fibrosis markers (COX-2, mPGES-1, TGF-beta, collagen I).
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| ADME/Pharmacokinetics |
CAY-10590 exhibits favorable pharmacokinetic properties. After intraperitoneal administration, the compound is rapidly absorbed, reaching peak plasma concentration (Cmax) within 0.5-1 hour. The terminal elimination half-life (t1/2) is approximately 2-4 hours in mice. The compound has a volume of distribution (Vd) of 1-2 L/kg, indicating good tissue penetration, and a total body clearance (CL) of 1-2 L/h/kg. Oral bioavailability is low (approximately 5-10%) due to poor aqueous solubility and first-pass metabolism. Protein binding is moderate (~80-90% in mouse plasma). The compound is primarily metabolized in the liver via oxidation and glucuronidation, and metabolites are excreted in both urine and feces. For intravenous administration, the half-life is shorter (1-2 hours) due to rapid distribution. Detailed human PK data are not available.
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| Toxicity/Toxicokinetics |
Toxicological data for CAY-10590 are primarily from preclinical animal studies. In mice, repeated daily doses of up to 10 mg/kg for 4-8 weeks were well tolerated, with no significant weight loss, abnormal clinical signs, or mortality. No major organ toxicity (liver, kidney, heart) was observed by histopathology. At higher doses (e.g., 50 mg/kg), mild elevations in liver enzymes (ALT, AST) and renal biomarkers (BUN, creatinine) may occur, along with gastrointestinal disturbances (diarrhea, reduced food intake). Genotoxicity studies are limited, but the compound does not have structural alerts for genotoxicity. No chronic toxicity or carcinogenicity data are available as CAY-10590 is a research chemical and not intended for human use. Care should be taken to avoid inhalation or skin contact, as the compound may be an irritant.
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| References | |
| Additional Infomation |
CAY-10590 is a research-grade sPLA2 inhibitor not approved for clinical use. It is supplied as a white to off-white solid powder with a purity of ≥98% (typically >98% by HPLC). The molecular formula is C21H33NO3 and the molecular weight is 347.49. The compound is soluble in DMSO (20 mg/mL), DMF (25 mg/mL), and ethanol (30 mg/mL), but has limited aqueous solubility. It should be stored at -20degC as a powder for up to 3 years, and stock solutions in DMSO should be stored at -80degC for up to 6 months. CAY-10590 is a useful tool for investigating the role of sPLA2 in inflammation, and for validating sPLA2 as a therapeutic target in chronic inflammatory diseases. Synonyms include GK115. The compound is not intended for diagnostic or therapeutic use, and is for laboratory research only.
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| Molecular Formula |
C21H33NO3
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| Molecular Weight |
347.491626501083
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| Exact Mass |
347.246
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| CAS # |
1101136-50-8
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| PubChem CID |
44563080
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| Appearance |
White to off-white solid powder
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| Density |
1.0±0.1 g/cm3
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| Boiling Point |
567.8±43.0 °C at 760 mmHg
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| Flash Point |
297.2±28.2 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.511
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| LogP |
4.55
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
14
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| Heavy Atom Count |
25
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| Complexity |
364
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CCCC[C@H](CCC(=O)O)NC(=O)CCCCCCC1=CC=CC=C1
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| InChi Key |
ANTPELWBOPVWPH-LJQANCHMSA-N
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| InChi Code |
InChI=1S/C21H33NO3/c1-2-3-14-19(16-17-21(24)25)22-20(23)15-10-5-4-7-11-18-12-8-6-9-13-18/h6,8-9,12-13,19H,2-5,7,10-11,14-17H2,1H3,(H,22,23)(H,24,25)/t19-/m1/s1
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| Chemical Name |
(4R)-4-(7-phenylheptanoylamino)octanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8778 mL | 14.3889 mL | 28.7778 mL | |
| 5 mM | 0.5756 mL | 2.8778 mL | 5.7556 mL | |
| 10 mM | 0.2878 mL | 1.4389 mL | 2.8778 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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