2. Immunology/Inflammation
  3. Interleukin Related
  4. Acloproxalap

Acloproxalap (ADX-629) is an orally active reactive aldehyde species (RASP) inhibitor. Acloproxalap binds covalently to free aldehydes, sequesters reactive aldehyde species, malondialdehyde, acetaldehyde and preformed malondialdehyde-acetaldehyde adducts, and reduces elevated RASP levels. Acloproxalap decreases the formation of aldehyde adducts, reduces liver and serum triglyceride levels, hepatic fat accumulation, circulating anti-malondialdehyde-acetaldehyde adduct antibody levels, and inhibits the release of IL-6 and MCP-1. Acloproxalap improves cell viability of liver slices exposed to ethanol. Acloproxalap blocks ethanol-induced damage in animal models of alcoholic liver disease. Acloproxalap is applicable to research related to alcoholic liver disease, alcoholic fatty liver disease, non-alcoholic steatohepatitis, chronic cough, rheumatoid arthritis, ulcerative colitis and mild atopic asthma.

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Acloproxalap

Acloproxalap Chemical Structure

CAS No. : 1824609-67-7

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Acloproxalap Related Antibodies

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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

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  • Purity & Documentation

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Description

Acloproxalap (ADX-629) is an orally active reactive aldehyde species (RASP) inhibitor. Acloproxalap binds covalently to free aldehydes, sequesters reactive aldehyde species, malondialdehyde, acetaldehyde and preformed malondialdehyde-acetaldehyde adducts, and reduces elevated RASP levels. Acloproxalap decreases the formation of aldehyde adducts, reduces liver and serum triglyceride levels, hepatic fat accumulation, circulating anti-malondialdehyde-acetaldehyde adduct antibody levels, and inhibits the release of IL-6 and MCP-1. Acloproxalap improves cell viability of liver slices exposed to ethanol. Acloproxalap blocks ethanol-induced damage in animal models of alcoholic liver disease. Acloproxalap is applicable to research related to alcoholic liver disease, alcoholic fatty liver disease, non-alcoholic steatohepatitis, chronic cough, rheumatoid arthritis, ulcerative colitis and mild atopic asthma[1][2][3][4][5].

IC50 & Target[4]

IL-6

 

In Vitro

ADX-629 (0.1-100 μM; 24-72 h) reduces acetaldehyde levels in precision-cut liver slices from C57/BL6 mice exposed to 25 mM ethanol. Among the tested conditions, 0.1 μM (24 h) induces the greatest reduction within 24 hours, and the reduction effect of 1 μM (72 h) is statistically significant at the 72-hour time point[2].
ADX-629 (0.1-100 μM; 24-72 h) reduces ethanol-induced elevation of triglycerides in precision liver slices from C57/BL6 mice. Among the tested conditions, 0.1 μM (24 h) produces the greatest reduction within 24 hours, while 1 μM (24, 48, and 72 h) significantly decreases triglyceride levels to the level of the control group at all three time points[2].
ADX-629 increases the cell viability of precision liver slices from C57/BL6 mice exposed to 25 mM ethanol, and this effect is detected by measuring lactate dehydrogenase and adenosine triphosphate levels[2].
Acloproxalap (0-200 μM; 30-minute pre-treatment) potently reduces FIB-MAA-induced IL-6 and MCP-1 release in PMA (HY-18739)-differentiated human monocytic U-937 macrophages; it exerts significant inhibitory effects at a concentration of 1 μM, reduces cytokine release to background levels at concentrations ≥10 μM, and shows no cytotoxicity at all tested doses[4].

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

Acloproxalap Related Antibodies

ELISA Assay[4]

Cell Line: PMA-differentiated U-937 human monocytic macrophages
Concentration: 0, 1, 10, 50, 100, 200 μM (30-minute pre-treatment)
Incubation Time: 30 min (pre-treatment); 24 h (FIB-MAA incubation)
Result: Significantly reduced IL-6 and MCP-1 release at 1 μM.
Reduced cytokine levels to background (unmodified fibrinogen) levels at concentrations ≥10 μM.
Showed no toxic effects, with >99% cell viability confirmed via LDH assay.
In Vivo

Acloproxalap (400 mg/kg; p.o.; single dose) administered at 400 mg/kg orally significantly reduces liver acetaldehyde (by 48.6%), liver triglycerides (by 47.4%), liver MAA antigen (by 41.8%), serum anti-MAA antibodies (by 68.0%), serum ALT (by 40.0%), liver IFN-γ (by 54.5%), and liver MCP-1 (by 67.1%) in a mouse chronic/binge model of alcoholic liver disease, while increasing serum acetaldehyde[1].

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

Animal Model: C57/BL6 (10- to 12-week-old female, ≥20 g, chronic/binge alcoholic liver disease model)[1]
Dosage: 400 mg/kg
Administration: p.o.; single dose
Result: Increased serum acetaldehyde to 37.5 µM from 8.3 µM in ethanol-only mice.
Decreased liver acetaldehyde to 146.2 µM/mg from 284.3 µM/mg in ethanol-only mice.
Reduced serum triglyceride levels to 112.2 mg/dL from 166.2 mg/dL in ethanol-only mice.
Reduced liver triglyceride levels to 157.4 mg/dL/mg of protein from 299.0 mg/dL/mg of protein in ethanol-only mice.
Reduced Oil Red O staining integrated density significantly.
Reduced Bodipy staining integrated density significantly.
Reduced liver malondialdehyde-acetaldehyde (MAA) antigen levels to 3.2 from 5.5 in ethanol-only mice.
Reduced serum anti-MAA antibody levels to 74.3 relative units from 232.6 relative units in ethanol-only mice.
Reduced serum alanine aminotransferase (ALT) levels to 26.3 IU/L from 43.8 IU/L in ethanol-only mice.
Reduced liver interferon-γ (IFN-γ) levels to 3.0 pg/mL/mg from 6.6 pg/mL/mg in ethanol-only mice.
Reduced liver monocyte chemoattractant protein-1 (MCP-1) levels to 15.62 pg/mL/mg from 47.5 pg/mL/mg in ethanol-only mice.
Clinical Trial
Molecular Weight

202.25

Formula

C12H14N2O
CAS No.
Appearance

Solid

Color

Light yellow to yellow

SMILES

OC(C)(C)C1=NC2=C(C=C1N)C=CC=C2
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 100 mg/mL (494.44 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 4.9444 mL 24.7219 mL 49.4438 mL
5 mM 0.9889 mL 4.9444 mL 9.8888 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. 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)

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Volume
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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)

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C2

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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: ≥ 2.5 mg/mL (12.36 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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: ≥ 2.5 mg/mL (12.36 mM); Clear solution

    This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 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

Animal weight
(per animal)

g

Dosing volume
(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).
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. 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 4.9444 mL 24.7219 mL 49.4438 mL 123.6094 mL
5 mM 0.9889 mL 4.9444 mL 9.8888 mL 24.7219 mL
10 mM 0.4944 mL 2.4722 mL 4.9444 mL 12.3609 mL
15 mM 0.3296 mL 1.6481 mL 3.2963 mL 8.2406 mL
20 mM 0.2472 mL 1.2361 mL 2.4722 mL 6.1805 mL
25 mM 0.1978 mL 0.9889 mL 1.9778 mL 4.9444 mL
30 mM 0.1648 mL 0.8241 mL 1.6481 mL 4.1203 mL
40 mM 0.1236 mL 0.6180 mL 1.2361 mL 3.0902 mL
50 mM 0.0989 mL 0.4944 mL 0.9889 mL 2.4722 mL
60 mM 0.0824 mL 0.4120 mL 0.8241 mL 2.0602 mL
80 mM 0.0618 mL 0.3090 mL 0.6180 mL 1.5451 mL
100 mM 0.0494 mL 0.2472 mL 0.4944 mL 1.2361 mL
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Acloproxalap 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:

Acloproxalap1824609-67-7ADX-629ADX629ADX 629Interleukin RelatedILmalondialdehyde-acetaldehyde adductsmalondialdehydealcoholic liver diseaseU-937 human monocytic macrophagesreactive aldehyde speciesC57/BL6 mouse precision cut liver slicesmacrophagesacetaldehydeliver slicesnon-alcoholic steatohepatitisInhibitorinhibitorinhibit

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