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| Targets |
Fuzapladib targets multiple pathways involved in the inflammatory response. It is a potent inhibitor of phospholipase A2 (PLA2), a key enzyme in the release of arachidonic acid, a precursor for pro-inflammatory mediators. Additionally, it acts as an orally active inhibitor of leukocyte-function-associated antigen type 1 (LFA-1) activation. By inhibiting LFA-1, a cell adhesion molecule, it blocks the adhesion of inflammatory cells to vascular endothelial cells and their subsequent infiltration into tissues. This dual mechanism contributes to its potent anti-inflammatory effects.
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| ln Vitro |
When LPS stimulation is applied to HL-60 cells and HUVECs, fuzapladib (IS-741) (1 μM, 3 h) can dramatically decrease labeling [3].
In vitro, fuzapladib (IS-741) at a concentration of 1 μM for 3 hours significantly inhibits the adhesion of HL-60 cells (a human leukemia cell line) to human umbilical vein endothelial cells (HUVECs) after lipopolysaccharide (LPS) stimulation. This effect is mediated through the inhibition of the expression of Mac-1, a cell adhesion molecule. These findings confirm its activity in blocking the adhesion of inflammatory cells to the endothelium. |
| ln Vivo |
Fuzapladib (IS-741) (po, 50 mg/kg, 7 days) effectively explains trinitrobenzene sulfonate (TNBS) ileitis by inhibiting the inflammatory response of circulating neutrophils [4].
In vivo, oral administration of fuzapladib (IS-741) at 50 mg/kg significantly reduces small intestinal myeloperoxidase (MPO) activity and IL-8 levels in a rat model of ileitis induced by trinitrobenzene sulfonic acid (TNBS). This treatment also decreases the infiltration of polymorphonuclear cells and Mac-1-positive cells into inflammatory lesions, effectively alleviating the induced ileitis. These results demonstrate its potent anti-inflammatory efficacy in a preclinical model of intestinal inflammation. |
| Enzyme Assay |
In vitro enzyme assays for fuzapladib typically involve measuring its inhibition of phospholipase A2 (PLA2) activity using purified enzyme preparations. The compound is incubated with PLA2 and a phospholipid substrate, and the release of arachidonic acid is measured to determine its inhibitory potency. Its inhibition of LFA-1 activation can be assessed in cell adhesion assays.
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| Cell Assay |
In vitro cell-based assays for fuzapladib assess its effect on leukocyte adhesion. A key method involves treating HL-60 cells with 1 μM fuzapladib for 3 hours and then measuring their adhesion to human umbilical vein endothelial cells (HUVECs) under inflammatory conditions induced by LPS. The compound's ability to inhibit Mac-1 expression and cell adhesion is a primary readout in these assays.
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| Animal Protocol |
Animal/Disease Models: Rat [4]
Doses: 50 mg/kg Route of Administration: Po; 7 days Experimental Results: Dramatically diminished rat ileal myeloperoxidase (MPO) activity and mucosal IL-8 levels, diminished polymorphonuclear cells and Infiltration of Mac-1 positive cells into inflammatory lesions effectively alleviates trinitrobenzene sulfonic acid (TNBS)-induced ileitis. In vivo animal experiments for fuzapladib have been conducted in a rat model of trinitrobenzene sulfonic acid (TNBS)-induced ileitis. Rats are orally administered fuzapladib at 50 mg/kg. Efficacy is assessed by measuring MPO activity and IL-8 levels in the small intestine, as well as by histopathological analysis of inflammatory cell infiltration. |
| ADME/Pharmacokinetics |
Fuzapladib is an orally active compound. It has a molecular weight of 379.40 and is soluble in DMSO (3.79 mg/mL, 10 mM). The compound is typically stored as a powder at -20°C for long-term stability. Its pharmacokinetic properties have been characterized in preclinical studies.
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| Toxicity/Toxicokinetics |
Specific toxicity data for fuzapladib is not extensively detailed in the search results. As an anti-inflammatory agent in development, its safety profile is part of ongoing research. The compound is for research use only and is not intended for human or veterinary use. Standard safety precautions should be taken when handling this compound.
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| References | |
| Additional Infomation |
See also: IS-741 Sodium (Active Part).
Fuzapladib (IS-741) is an orally active small-molecule inhibitor of phospholipase A2 (PLA2) and LFA-1 activation. It exerts anti-inflammatory effects by inhibiting the migration of leukocytes to sites of inflammation. The compound has been studied for the treatment of acute pancreatitis and other inflammatory conditions. It is a research compound and is not approved for clinical use. |
| Molecular Formula |
C15H20F3N3O3S
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|---|---|
| Molecular Weight |
379.3978
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| Exact Mass |
379.118
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| CAS # |
141283-87-6
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| Related CAS # |
Fuzapladib sodium;141284-73-3
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| PubChem CID |
154529
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| Appearance |
White to off-white solid powder
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| Density |
1.411g/cm3
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| Index of Refraction |
1.548
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| LogP |
5.184
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
557
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
TUWCZRFHNIOVTC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H20F3N3O3S/c1-2-25(23,24)21-13-12(8-11(9-19-13)15(16,17)18)20-14(22)10-6-4-3-5-7-10/h8-10H,2-7H2,1H3,(H,19,21)(H,20,22)
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| Chemical Name |
N-[2-(ethylsulfonylamino)-5-(trifluoromethyl)pyridin-3-yl]cyclohexanecarboxamide
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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 Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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 : ~100 mg/mL (~263.57 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.59 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.59 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6357 mL | 13.1787 mL | 26.3574 mL | |
| 5 mM | 0.5271 mL | 2.6357 mL | 5.2715 mL | |
| 10 mM | 0.2636 mL | 1.3179 mL | 2.6357 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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