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| Targets |
S100A8/A9 (calprotectin) and its receptors RAGE and TLR4. ABR-238901 is a small-molecule blocker that inhibits the interaction of S100A8/A9 with its receptors RAGE and TLR4. S100A8/A9 is a heterodimeric protein complex that functions as a DAMP and promotes inflammatory responses through RAGE and TLR4 activation. By blocking this interaction, ABR-238901 reduces S100A8/A9-mediated inflammation.
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| ln Vitro |
ABR-238901 is an orally active and potent S100A8/A9 blocker that inhibits the interaction of S100A8/A9 with its receptors RAGE and TLR4. By blocking this interaction, the compound reduces S100A8/A9-mediated inflammatory signaling. Its activity has been characterized in biochemical and cellular assays demonstrating inhibition of S100A8/A9-induced pro-inflammatory responses.
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| ln Vivo |
MDSCs treated with ABR-238901 (30 mg/kg/day; gavage; for 3 weeks) exhibit decreased angiogenesis as well as IL6 and IL10 levels[1]. When paired with bortezomib (0.6 mg/kg; subcutaneous injection; twice weekly), ABR-238901 (30 mg/kg/day; gavage) decreased the amount of tumor when compared to therapy with either drug alone[1]. In C57BL/6NRJ mice, ABR-238901 (30 mg/kg; intraperitoneal; for the first three days; then, continuing oral daily dosage; for 21 days) causes myocardial ischemia brought on by permanent coronary artery ligation, which progressively deteriorates cardiac function and speeds up left ventricular remodeling. In the initial three days following a myocardial infarction (MI), ABR-238901 treatment reduces inflammatory damage and fosters a healing milieu[2].
In vivo, ABR-238901 is an orally active S100A8/A9 blocker. By inhibiting the interaction of S100A8/A9 with RAGE and TLR4, it reduces S100A8/A9-mediated inflammation. Its oral bioavailability makes it suitable for chronic administration in animal models of inflammatory diseases. The compound's efficacy would be assessed in models of inflammation, autoimmunity, and other S100A8/A9-mediated diseases. |
| Enzyme Assay |
In vitro binding assays for ABR-238901 are used to characterize its ability to inhibit the interaction between S100A8/A9 and its receptors RAGE and TLR4. These assays typically involve ELISA-based or surface plasmon resonance-based binding studies where the compound's ability to disrupt the S100A8/A9-receptor interaction is measured.
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| Cell Assay |
In vitro cellular assays for ABR-238901 involve treating immune cells (such as macrophages or monocytes) with the compound and measuring its ability to inhibit S100A8/A9-induced inflammatory responses. Readouts include inhibition of pro-inflammatory cytokine production (e.g., TNF-α, IL-6, IL-1β), NF-κB activation, and other markers of S100A8/A9-mediated signaling. These assays confirm the compound's ability to block S100A8/A9 activity in a cellular context.
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| Animal Protocol |
Animal/Disease Models: C57BL/KaLwRij mice with 5T33MMvv cells[1]
Doses: 30 mg/kg Route of Administration: Gavage; daily; for 3 weeks Experimental Results: Caused less angiogenesis. Caused less IL6 and IL10 in myeloid-derived suppressor cells (MDSCs). In vivo efficacy of ABR-238901 would be evaluated in animal models of inflammatory diseases where S100A8/A9 plays a pathogenic role. The compound is orally active, making it suitable for oral administration. Efficacy endpoints would include reduction of inflammatory markers, improvement in disease severity scores, and tissue pathology in models of conditions such as inflammatory bowel disease, arthritis, and other S100A8/A9-mediated inflammatory diseases. |
| ADME/Pharmacokinetics |
ABR-238901 has a molecular formula of C11H9BrClN3O4S and a molecular weight of 394.63. It is soluble in DMSO (79 mg/mL, 200.18 mM). As an orally active small molecule, its pharmacokinetic properties support oral dosing. The compound is supplied with high purity (>98%) and is for research use only.
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| Toxicity/Toxicokinetics |
No specific toxicity data is available for ABR-238901. As an S100A8/A9 blocker, its safety profile would be an important consideration for therapeutic applications. Potential toxicities could be related to its effects on S100A8/A9-mediated immune functions. Standard preclinical safety studies would be required to evaluate its safety for potential therapeutic applications.
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| References |
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| Additional Infomation |
ABR-238901 (CAS#: 1638200-22-2) is an orally active and potent S100A8/A9 blocker that inhibits the interaction of S100A8/A9 with its receptors RAGE and TLR4. It has a molecular formula of C11H9BrClN3O4S and a molecular weight of 394.63. The compound is a research tool for studying S100A8/A9-mediated inflammatory diseases and is not approved for clinical use.
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| Molecular Formula |
C11H9BRCLN3O4S
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|---|---|
| Molecular Weight |
394.63
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| Exact Mass |
392.918
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| CAS # |
1638200-22-2
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| PubChem CID |
86280668
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| Appearance |
Off-white to yellow solid powder
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| LogP |
1.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
587
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=NC(OC)=C(Br)C=C1S(NC1=C(O)C(Cl)=CN=C1)(=O)=O
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| InChi Key |
IXVPHMAWVYMOQL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C11H9BrClN3O4S/c1-20-11-7(12)2-6(3-15-11)21(18,19)16-9-5-14-4-8(13)10(9)17/h2-5,16H,1H3,(H,14,17)
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| Chemical Name |
5-bromo-N-(5-chloro-4-oxo-1H-pyridin-3-yl)-6-methoxypyridine-3-sulfonamide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 33.33 mg/mL (84.46 mM)
H2O: < 0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5340 mL | 12.6701 mL | 25.3402 mL | |
| 5 mM | 0.5068 mL | 2.5340 mL | 5.0680 mL | |
| 10 mM | 0.2534 mL | 1.2670 mL | 2.5340 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.
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