2. PROTAC Immunology/Inflammation
  3. Molecular Glues NOD-like Receptor (NLR) Interleukin Related
  4. NP3-253

NP3-253 is an orally active and brain-penetranted NLRP3 inflammasome inhibitor. NP3-253 functions as a molecular glue that prevents NACHT-subdomain rearrangements, locking NLRP3 in an inactive conformation. NP3-253 inhibits production of pro-inflammatory cytokines IL-1β and IL-18. NP3-253 can be used for the research of inflammation and neurological disease, suah as peritonitis.

For research use only. We do not sell to patients.

NP3-253

NP3-253 Chemical Structure

CAS No. : 2557349-50-3

Size Price Stock Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO
ready for reconstitution
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NP3-253 Related Antibodies

Top Publications Citing Use of Products

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NLRP3 NLRP1 NOD1 NOD2

View All Interleukin Related Isoform Specific Products:

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IL-1 IL-2 IL-3 IL-4 IL-5 IL-6 IL-8 IL-10 IL-12 IL-13 IL-15 IL-17 IL-23 IL-7 IL-33 IL-22 IL-18

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

NP3-253 is an orally active and brain-penetranted NLRP3 inflammasome inhibitor. NP3-253 functions as a molecular glue that prevents NACHT-subdomain rearrangements, locking NLRP3 in an inactive conformation. NP3-253 inhibits production of pro-inflammatory cytokines IL-1β and IL-18. NP3-253 can be used for the research of inflammation and neurological disease, suah as peritonitis[1].

IC50 & Target[1]

NLRP3 inflammasome

 

IL-1β

 

IL-18

 

In Vitro

NP3-253 potently inhibits NLRP3-mediated IL-1β secretion in PMA (HY-18739)-differentiated THP-1 cells with an IC50 of 0.5 ± 0.1 nM, and does not inhibit NF-κB-mediated TNF-α secretion[1].
NP3-253 potently inhibits NLRP3-mediated IL-1β secretion in human whole blood with an IC50 of 7 ± 2 nM[1].
NP3-253 does not inhibit NLRC4 inflammasome-mediated IL-1β secretion in NLRC4-overexpressing THP-1 cells at concentrations up to >33 μM, demonstrating inflammasome selectivity[1].
NP3-253 (10 μM; 2 h) has a low efflux ratio of 2.5 in MDCK-MDR1 cells, indicating it is not a strong substrate for human P-glycoprotein[1].
NP3-253 (0.5-25 μM; 10-15 min) does not inhibit human CYP3A4 or CYP2C9 at concentrations up to >25 μM, but potently inhibits CYP2D6 with an IC50 of <0.5 μM[1].
NP3-253 inhibits hERG channel binding with an IC50 of 6.49 μM, suggesting a potential cardiac liability[1].
NP3-253 shows high selectivity across a panel of 29 off-target enzymes, receptors, and ion channels tested up to 10 μM, with only weak binding to muscarinic receptor M2 (IC50 = 9.9 μM) and serotonin transporter 5HTT (IC50 = 3.8 μM)[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

NP3-253 Related Antibodies
In Vivo

NP3-253 (0.0083-3 mg/kg; p.o.; single dose 3 hours prior to LPS priming) potently inhibits LPS (HY-D1056)-induced IL-1β production in mouse peritonitis in a dose-dependent manner, with 99.4 and 99.6% inhibition at doses of 3 and 2 mg/kg, respectively[1].
NP3-253 (10 mg/kg; p.o.; single dose 22 hours prior to LPS priming) fully inhibits LPS-induced IL-1β production in mouse peritonitis[1].
NP3-253 (20 mg/kg; p.o.; single dose 1 hour prior to LPS injection) completely inhibits LPS-induced IL-18 production in mouse plasma[1].
NP3-253 (0.02-2 mg/kg; p.o.; single dose 1 hour prior to second LPS injection) inhibits LPS-induced IL-1β production in mouse CSF and serum in a dose-dependent manner, with 96.5% inhibition in CSF at 2 mg/kg, and reduces downstream Ccl20 gene expression in brain tissue without affecting Il1b gene expression[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Peritonitis C57BL/6JRj (female, 8-12 weeks old)[1]
Dosage: 0.0083, 0.05, 0.3, 2, 3 mg/kg
Administration: P.o.; single dose 3 hours prior to LPS priming
Result: Achieved 99.4% inhibition of IL-1β in peritoneal washout fluid, with a terminal blood concentration of 0.597 ± 0.029 μM and a terminal brain concentration of 0.676 ± 0.074 μM (3 mg/kg).
Achieved 99.6 ± 0.2% inhibition of IL-1β in peritoneal washout fluid, with a serum blood concentration of 0.479 ± 0.074 μM and a brain concentration of 0.564 ± 0.1 μM (2 mg/kg).
Achieved 98.3 ± 1.9% inhibition of IL-1β in peritoneal washout fluid, with a serum blood concentration of 0.076 ± 0.011 μM and a brain concentration of 0.087 ± 0.015 μM (0.3 mg/kg).
Achieved 43.9 ± 22.4% inhibition of IL-1β in peritoneal washout fluid, with a serum blood concentration of 0.011 ± 0.001 μM and a brain concentration of 0.013 ± 0.001 μM (0.05 mg/kg).
Achieved 16.0 ± 30.0% inhibition of IL-1β in peritoneal washout fluid, with a serum blood concentration of 0.002 ± 0.0001 μM and a brain concentration of 0.0002 ± 0.0003 μM (0.0083 mg/kg).
Molecular Weight

380.41

Formula

C19H23F3N4O
CAS No.
Appearance

Solid

Color

Off-white to light brown

SMILES

CC1=CC(C(F)(F)F)=CC(O)=C1C2=NN=C(N[C@@H]3CCCN(CC)C3)C=C2
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (262.87 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 2.6287 mL 13.1437 mL 26.2874 mL
5 mM 0.5257 mL 2.6287 mL 5.2575 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
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Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

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Volume (start)

V1

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C2

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Volume (final)

V2

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% Saline

    Solubility: ≥ 5 mg/mL (13.14 mM); Clear solution

    This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

    Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
  • Protocol 2

    Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in Saline)

    Solubility: ≥ 5 mg/mL (13.14 mM); Clear solution

    This protocol yields a clear solution of ≥ 5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

    Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

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g

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(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO +
% 
+
%
Tween-80 +
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.6287 mL 13.1437 mL 26.2874 mL 65.7186 mL
5 mM 0.5257 mL 2.6287 mL 5.2575 mL 13.1437 mL
10 mM 0.2629 mL 1.3144 mL 2.6287 mL 6.5719 mL
15 mM 0.1752 mL 0.8762 mL 1.7525 mL 4.3812 mL
20 mM 0.1314 mL 0.6572 mL 1.3144 mL 3.2859 mL
25 mM 0.1051 mL 0.5257 mL 1.0515 mL 2.6287 mL
30 mM 0.0876 mL 0.4381 mL 0.8762 mL 2.1906 mL
40 mM 0.0657 mL 0.3286 mL 0.6572 mL 1.6430 mL
50 mM 0.0526 mL 0.2629 mL 0.5257 mL 1.3144 mL
60 mM 0.0438 mL 0.2191 mL 0.4381 mL 1.0953 mL
80 mM 0.0329 mL 0.1643 mL 0.3286 mL 0.8215 mL
100 mM 0.0263 mL 0.1314 mL 0.2629 mL 0.6572 mL
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NP3-253 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

NP3-2532557349-50-3Molecular GluesNOD-like Receptor (NLR)Interleukin RelatedILNACHT-subdomainNLRP3 inflammasomeinterleukin-1βNLRC4U937interleukin-18MDCK-KO cell monolayershERG channelpyroptotic cell deathTHP-1 cellsInhibitorinhibitorinhibit

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