1. MAPK/ERK Pathway Stem Cell/Wnt NF-κB Immunology/Inflammation Apoptosis
  2. p38 MAPK ERK NF-κB Interleukin Related TNF Receptor
  3. Anti-inflammatory agent 35

Anti-inflammatory agent 35 (compound 5a27) is an orally active curcumin analogue with anti-inflammatory activity. Anti-inflammatory agent 35 blocks mitogen-activated protein kinase (MAPK) signaling and p65 nuclear translocation of NF-kB. Anti-inflammatory agent 35 also inhibits yellow neutrophil infiltration and pro-inflammatory cytokine production. Anti-inflammatory agent 35 significantly attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI) in vivo.

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Anti-inflammatory agent 35 Chemical Structure

Anti-inflammatory agent 35 Chemical Structure

CAS No. : 2293951-00-3

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Description

Anti-inflammatory agent 35 (compound 5a27) is an orally active curcumin analogue with anti-inflammatory activity. Anti-inflammatory agent 35 blocks mitogen-activated protein kinase (MAPK) signaling and p65 nuclear translocation of NF-kB. Anti-inflammatory agent 35 also inhibits yellow neutrophil infiltration and pro-inflammatory cytokine production. Anti-inflammatory agent 35 significantly attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI) in vivo[1].

IC50 & Target[1]

p38 MAPK

 

ERK

 

I-kappaBalpha

 

IL-6

 

p65

 

NF-κB

 

In Vitro

Anti-inflammatory agent 35 (compound 5a27) (10 μM; 30 min) inhibits the production of proinflammatory cytokines (IL-6, TNF-α) induced by LPS (0.5 μg/mL; 24 h) without cytotoxicity in mouse primary macrophages (MPMs). Anti-inflammatory agent 35 inhibits the production of IL-6, TNF-α with IC50s of 2.23 μM and 2.40 μM, respectively[1].
Anti-inflammatory agent 35 (10 μM; 30 min) significantly inhibits LPS-induced activation in RAW 264.7 mouse macrophages. And it markedly inhibits p-p38 and p-ERK, decreases IκB level, indicating the suppression of MAPK and NF-κB signaling[1].

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

Western Blot Analysis[1]

Cell Line: RAW 264.7 mouse macrophages
Concentration: 10 μM
Incubation Time: 30 min; followed by incubation with 0.5 μg/mL LPS for another 30 min
Result: Decreased the phosphorylation of p38 and ERK. And down-regulated IκB (inhibitor of NF-κB), inhibits the transcription of TNF-α, IL-6, IL-1β, ICAM-1.
In Vivo

Anti-inflammatory agent 35 (compound 5a27) (50 mg/kg; po; single dose, monitored 0-25 min) has a better bioavailability than curcumin (HY-N0005)[1].
Anti-inflammatory agent 35 (10 mg/kg; ip; once daily for 1 week) improves LPS-induced ALI by inhibiting inflammation in mice model[1].

The pharmacokinetic parameters in rats[1]

Route Dose (mg/kg) AUC(0-t) (μg/L·h) AUC(0-∞) (μg/L·h) MRT(0-t) (h) MRT(0-∞) (h) t1/2 (h) Tmax (h) CLz/F (L/h/kg) Vz/F (L/kg) Cmax
p.o 50 231.2 325.6 7.8 12.3 6.7 3.3 5062.6 827.1 113.3
i.v 5 34.3 122.4 11.3 19.9 0.2 0.1 404.4 59.5 16.4

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

Animal Model: ALI mouse model (C57BL/6 mice)[1]
Dosage: 10 mg/kg
Administration: Intraperitoneal injection, once daily for 1 week; 30 min later every dose, followed by 5 mg/kg LPS, intratracheal injection
Result: Significantly normalized the wet/dry ratio of lungs.
Molecular Weight

495.52

Formula

C27H29NO8

CAS No.
Appearance

Solid

Color

White to off-white

SMILES

CC(OC1=CC=C(/C=C/C(N2C(/C(CCC2)=C/C3=CC(OC)=C(OC)C(OC)=C3)=O)=O)C=C1OC)=O

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 : 16.67 mg/mL (33.64 mM; ultrasonic and warming and heat to 60°C; 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 2.0181 mL 10.0904 mL 20.1808 mL
5 mM 0.4036 mL 2.0181 mL 4.0362 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.

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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    90% Corn Oil

    Solubility: ≥ 1.67 mg/mL (3.37 mM); Clear solution

    This protocol yields a clear solution of ≥ 1.67 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (16.7 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
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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 2.0181 mL 10.0904 mL 20.1808 mL 50.4521 mL
5 mM 0.4036 mL 2.0181 mL 4.0362 mL 10.0904 mL
10 mM 0.2018 mL 1.0090 mL 2.0181 mL 5.0452 mL
15 mM 0.1345 mL 0.6727 mL 1.3454 mL 3.3635 mL
20 mM 0.1009 mL 0.5045 mL 1.0090 mL 2.5226 mL
25 mM 0.0807 mL 0.4036 mL 0.8072 mL 2.0181 mL
30 mM 0.0673 mL 0.3363 mL 0.6727 mL 1.6817 mL
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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.

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Anti-inflammatory agent 35
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