CY-09

Catalog No.S5774

CY-09 Chemical Structure

Molecular Weight(MW): 423.43

CY-09 is a specific NLRP3 inflammasome inhibitor that directly targeted NLRP3 itself。 It is tested against the five major cytochrome P450 enzymes 1A2, 2C9, 2C19, 2D6, and 3A4 with half maximal inhibitory concentration (IC50) values of 18.9, 8.18, >50, >50, and 26.0 µM, respectively.

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Biological Activity

Description CY-09 is a specific NLRP3 inflammasome inhibitor that directly targeted NLRP3 itself。 It is tested against the five major cytochrome P450 enzymes 1A2, 2C9, 2C19, 2D6, and 3A4 with half maximal inhibitory concentration (IC50) values of 18.9, 8.18, >50, >50, and 26.0 µM, respectively.
Targets
NLRP3 inflammasome [1]
()
In vitro

CY-09 specifically blocks NLRP3 activation in macrophages. CY-09 inhibits NLRP3 oligomerization and inflammasome assembly. CY-09 directly binds to NLRP3 and inhibits its ATPase activity. The metabolic stability of CY-09 was first evaluated using human and mouse liver microsomes, exhibiting favorable stability with the half-life >145 min for both human and mouse microsomes. The metabolic stability of CY-09 was first evaluated using human and mouse liver microsomes, exhibiting favorable stability with the half-life >145 min for both human and mouse microsomes, which exhibited low risk of drug-drug interactions[1].

In vivo CY-09 inhibits NLRP3 activation in vivo and prevents neonatal lethality in a mouse model of CAPS. In pharmacokinetic studies evaluted in C57BL/6J mice administered a single i.v. or oral dose, CY-09 exhibits favorable pharmacokinetics, with a half-life of 2.4 h, an area under the curve of 8,232 (h·ng)/ml, and bioavailability of 72%. CY-09 reverses metabolic disorders in diabetic mice by inhibition of NLRP3-dependent inflammation. CY-09 treatment has remarkable beneficial effects for metainflammation, hyperglycemia, and insulin resistance in diabetic mice[1].

Protocol

Cell Research:

[1]

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  • Cell lines: BMDMs and PBMCs
  • Concentrations: 1, 5, and 10 μM
  • Incubation Time: 30 min
  • Method:

    5 × 105/ml BMDMs and 6 × 106/ml PBMCs were plated in 12-well plates. The following morning, the medium was replaced, and cells were stimulated with 50 ng/ml LPS or 400 ng/ml Pam3CSK4 (for noncanonical inflammasome activation) for 3 h. After that, CY-09 or other inhibitors were added into the culture for another 30 min, and then the cells were stimulated for 4 h with MSU (150 µg/ml), Salmonella typhimurium (multiplicity of infection) or for 30 min with ATP (2.5 mM) or nigericin (10 µM). Cells were transfected with poly(dA:dT) (0.5 µg/ml) for 4 h or LPS (500 ng/ml) overnight. Cell extracts and precipitated supernatants were analyzed by immunoblot.


    (Only for Reference)
Animal Research:

[1]

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  • Animal Models: C57BL/6J mice
  • Formulation: 10% DMSO, 10% Solutol HS 15, and 80% saline
  • Dosages: 5 and 10 mg/kg
  • Administration: i.v. and oral administration
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 85 mg/mL (200.74 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 423.43
Formula

C19H12F3NO3S2

CAS No. 1073612-91-5
Storage powder
in solvent
Synonyms N/A

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID