| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
Purity: ≥98%
| Targets |
The primary molecular target is the S100A9 protein, typically found as a heterodimer with S100A8 (forming calprotectin), predominantly expressed by myeloid cells such as neutrophils and monocytes. Paquinimod binds to S100A9, inducing a conformational change that prevents its engagement with TLR4 and RAGE. This blockade of the S100A9-TLR4/RAGE signaling axis disrupts downstream inflammatory cascades, including the MyD88-dependent pathway and subsequent NF-κB activation.
|
|---|---|
| ln Vitro |
Paquinimod exerts its immunomodulatory effects by inhibiting the S100A9 signaling pathway. By binding to S100A9, the compound prevents its interaction with TLR4 and RAGE, blocking the MyD88-dependent pathway and subsequent NF-κB activation. This results in a significant reduction in the production of pro-inflammatory cytokines and chemokines, decreased infiltration of myeloid cells into inflamed tissues, and attenuation of fibrotic processes. In preclinical models, blocking S100A9 signaling with Paquinimod has shown both beneficial and detrimental effects depending on the disease context.
|
| ln Vivo |
The S100 family includes the calcium-binding protein S100A9. An immunomodulatory substance called paquinimod stops S100A9 from attaching to TLR-4. The pathology in experimental collagenase-induced osteoarthritis is reduced by prophylactic treatment with the S100A9 inhibitor Paquinimod[1]. In the NOD mouse, paquinimod is a strong inhibitor of the development of insulitis and diabetes. In order to evaluate the preventive effectiveness of Paquinimod on the development of diabetes in female NOD mice, groups of mice are given daily doses of Paquinimod at 0.04, 0.2, 1, and 5 mg/kg/day from week 10 to week 20. From 10 weeks of age to the experiment's endpoint at 40 weeks of age, glycosuria is examined once a week. The development of diabetes in the mice treated with paquinimod is clearly reduced in a dose-dependent manner[2].
In vivo, Paquinimod has demonstrated immunomodulatory activity in various preclinical models of inflammatory and autoimmune diseases. The compound is orally active and has been shown to reduce inflammation and fibrosis in animal models. However, studies have also shown that blocking S100A9 signaling using Paquinimod can result in increased tumor growth and a detrimental effect on anti-PD-L1 efficacy in certain tumor models, highlighting the complex and context-dependent role of S100A9 in immunity and disease. |
| Enzyme Assay |
In vitro receptor binding assays for Paquinimod involve measuring the compound's ability to bind to the S100A9 protein using surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). The binding affinity and kinetics of Paquinimod for S100A9 are determined by these methods. Cellular assays involve treating immune cells (such as macrophages or neutrophils) with Paquinimod and measuring the production of pro-inflammatory cytokines (such as TNF-α, IL-6, and IL-1β) in response to S100A9 stimulation. These assays confirm the compound's ability to inhibit S100A9-mediated inflammatory responses.
|
| Cell Assay |
In vitro cellular assays for Paquinimod are conducted using immune cells such as macrophages, monocytes, or neutrophils. Cells are treated with Paquinimod and then stimulated with S100A9 protein or other inflammatory stimuli. The production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and chemokines is measured by ELISA or multiplex assays. The compound's ability to inhibit S100A9-mediated inflammatory responses is assessed by measuring the reduction in cytokine production and the inhibition of NF-κB activation. These assays demonstrate the immunomodulatory activity of Paquinimod at the cellular level.
|
| Animal Protocol |
Mice
After being exposed to increasing concentrations of CO2, female NOD/MrkTac mice are cervically dislocated to induce unconsciousness. In order to examine how the Q-compound Paquinimod affects the onset of glycosuria and insulitis, mice are given daily doses of approximately 0.04, 0.2, 1, and 5 mg/kg body weight/day of Paquinimod dissolved in drinking water at varying concentrations. Paquinimod is administered to the mice beginning at either 10 or 15 weeks of age. In the various trials that are conducted, the length of the treatment varies from 5 to 23 weeks[2]. In vivo animal studies for Paquinimod typically involve administration to rodent models of inflammatory or autoimmune diseases, such as colitis, arthritis, or fibrosis models. The compound is administered orally at various doses, and disease severity is assessed by clinical scores, histopathological examination, and measurement of inflammatory markers in tissues and serum. Pharmacokinetic parameters are determined from serial blood sampling. These studies establish the efficacy and dose-response relationship of Paquinimod in various disease models. |
| ADME/Pharmacokinetics |
Pharmacokinetic studies of Paquinimod have confirmed its safety and pharmacokinetics in human clinical trials. The compound is orally active and shows good bioavailability. After oral administration, Paquinimod is absorbed and reaches peak plasma concentrations within a predictable timeframe. The compound is metabolized primarily in the liver, and its metabolites are excreted in urine and feces. The pharmacokinetic profile of Paquinimod supports once-daily or twice-daily dosing. The compound has been well tolerated in human clinical trials.
|
| Toxicity/Toxicokinetics |
Preclinical toxicity studies have established the safety profile of Paquinimod. The compound has been well tolerated in human clinical trials with no significant safety concerns reported. In animal studies, Paquinimod has shown a favorable safety profile at doses that produce immunomodulatory effects. The compound's mechanism of action—targeting S100A9, a DAMP molecule—suggests that it may have a favorable safety profile compared to broader immunosuppressive agents, as it specifically targets inflammatory pathways without causing generalized immunosuppression.
|
| References |
|
| Additional Infomation |
Paquinimod was developed to treat systemic lupus erythematosus (SLE), an autoimmune disease. SLE primarily affects women of childbearing age and presents with periodic flare-ups, often with relatively asymptomatic intervals between flare-ups. Current treatments for SLE include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antimalarial drugs, or cytotoxic agents such as cyclophosphamide. The autoimmune attack affects multiple organ systems, and as the disease progresses, many patients develop serious secondary complications, such as kidney disease.
Paquinimod (ABR-215757) is an orally active immunomodulator that has been evaluated in human clinical trials for various inflammatory and autoimmune diseases. Its primary mechanism of action is the targeted inhibition of the S100A9 protein, a critical damage-associated molecular pattern (DAMP) molecule implicated in a wide range of inflammatory and autoimmune diseases. By binding to S100A9, Paquinimod prevents its interaction with TLR4 and RAGE, disrupting downstream inflammatory cascades. The compound has been well tolerated in clinical trials, and its safety and pharmacokinetics have been confirmed in human studies. Further clinical development may be ongoing for specific indications. |
| Molecular Formula |
C21H22N2O3
|
|---|---|
| Molecular Weight |
350.42
|
| Exact Mass |
350.163
|
| Elemental Analysis |
C, 71.98; H, 6.33; N, 7.99; O, 13.70
|
| CAS # |
248282-01-1
|
| PubChem CID |
54684617
|
| Appearance |
White to off-white solid powder.
|
| Density |
1.267g/cm3
|
| Boiling Point |
487.259ºC at 760 mmHg
|
| Flash Point |
248.486ºC
|
| Vapour Pressure |
0mmHg at 25°C
|
| Index of Refraction |
1.648
|
| LogP |
3.473
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
3
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
26
|
| Complexity |
580
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
O([H])C1=C(C(N(C2C([H])=C([H])C([H])=C([H])C=2[H])C([H])([H])C([H])([H])[H])=O)C(N(C([H])([H])[H])C2=C([H])C([H])=C([H])C(C([H])([H])C([H])([H])[H])=C21)=O
|
| InChi Key |
DIKSYHCCYVYKRO-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H22N2O3/c1-4-14-10-9-13-16-17(14)19(24)18(20(25)22(16)3)21(26)23(5-2)15-11-7-6-8-12-15/h6-13,24H,4-5H2,1-3H3
|
| Chemical Name |
N,5-diethyl-4-hydroxy-1-methyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide
|
| Synonyms |
ABR‑215757; ABR 215757; ABR215757; Paquinimod.
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO : 62.5~70 mg/mL ( 178.36~199.76 mM )
Ethanol : ~17 mg/mL H2O : < 0.1 mg/mL |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.13 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (5.94 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (7.13 mM) Solubility in Formulation 4: 5 mg/mL (14.27 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8537 mL | 14.2686 mL | 28.5372 mL | |
| 5 mM | 0.5707 mL | 2.8537 mL | 5.7074 mL | |
| 10 mM | 0.2854 mL | 1.4269 mL | 2.8537 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.
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
