| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Feniralstat is a highly selective inhibitor of human plasma kallikrein (pKal). It shows minimal off-target effects, as it has no significant inhibitory activity against other related serine proteases, including human KLK1, human FXIa, and human factor XIIa, with all reported IC50 values exceeding 40 microM.
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| ln Vitro |
In vitro studies demonstrate that Feniralstat potently inhibits human plasma kallikrein with an IC50 of 6.7 nM. This high level of potency is measured in a standard biochemical assay using a fluorogenic substrate. In comparison to a known benchmark, the clinical candidate berotralstat (BCX7353) shows a more potent IC50 of 0.88 nM against the same target under similar conditions.
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| ln Vivo |
While many studies focus on its potent in vitro activity, published data on its in vivo efficacy is more limited. It is known to be a selective and highly efficient kallikrein inhibitor that can be used for researching immune system diseases and cardiovascular diseases, suggesting that in vivo models for these conditions have been employed, though specific protocols are not always detailed in standard product data sheets.
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| Enzyme Assay |
A typical non-cellular protocol involves measuring the inhibition of human plasma kallikrein (pKal) activity. Feniralstat is dissolved in an appropriate buffer (e.g., DMSO, then diluted). Purified human plasma kallikrein is incubated with varying concentrations of Feniralstat in a 96-well plate for 15 minutes. A fluorogenic substrate (e.g., H-D-Pro-Phe-Arg-AMC) is then added, and the increase in fluorescence is measured over time to determine residual enzyme activity and calculate IC50.
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| Cell Assay |
No specific cell-based experimental procedure for Feniralstat is standardly reported, as its primary target, plasma kallikrein, is a soluble enzyme in the blood. Its activity is best assessed in cell-free systems. However, its effects on cellular function can be studied downstream by adding it to cell cultures and measuring relevant outputs, such as the production of inflammatory mediators like bradykinin.
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| Animal Protocol |
Published in vivo protocols for Feniralstat are not widely available. For similar kallikrein inhibitors, a typical in vivo model involves oral administration to rodents in a model of induced vascular leakage or inflammatory pain. Animals are dosed with the inhibitor, and then a challenge such as carrageenan or formalin is administered, followed by measurement of paw edema or pain behaviors.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for Feniralstat is not widely available in its product documentation. As a small-molecule inhibitor designed for oral activity, it is expected to have properties that allow for systemic exposure when administered via oral gavage. In vivo studies would typically involve collecting plasma samples at various time points after drug administration to quantify exposure levels for PK/PD analysis.
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| Toxicity/Toxicokinetics |
No detailed toxicological data is provided for Feniralstat in these sources. As a research compound, it should be handled with standard precautions for laboratory chemicals. It is generally considered to have a favorable selectivity profile, which minimizes the risk of off-target mediated toxicity, but comprehensive safety studies are not publicly available for this research tool.
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| References | |
| Additional Infomation |
Feniralstat is a valuable pharmacological tool for investigating the plasma kallikrein-kinin system (KKS). This system is a key mediator of inflammation and vascular permeability, making the compound useful for studying conditions like hereditary angioedema (HAE). Its high selectivity for pKal over other proteases makes it an ideal probe for dissecting the specific role of this enzyme in complex biological pathways.
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| Molecular Formula |
C26H25F2N5O4
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|---|---|
| Molecular Weight |
509.50461268425
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| Exact Mass |
509.187
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| CAS # |
2166320-76-7
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| PubChem CID |
139301832
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| Appearance |
Off-white to gray solid powder
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| LogP |
1.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
37
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| Complexity |
851
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| Defined Atom Stereocenter Count |
0
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| SMILES |
FC1C=CC(N(C=1)CC1C=CC(=CC=1)CN1C=C(C(NCC2C(=C(C=CN=2)OC)F)=O)C(COC)=N1)=O
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| InChi Key |
ZRUFVDPYHLTYPD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H25F2N5O4/c1-36-16-22-20(26(35)30-11-21-25(28)23(37-2)9-10-29-21)15-33(31-22)13-18-5-3-17(4-6-18)12-32-14-19(27)7-8-24(32)34/h3-10,14-15H,11-13,16H2,1-2H3,(H,30,35)
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| Chemical Name |
N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-1-[[4-[(5-fluoro-2-oxopyridin-1-yl)methyl]phenyl]methyl]-3-(methoxymethyl)pyrazole-4-carboxamide
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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: 100 mg/mL (196.27 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.45 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 12.5 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: ≥ 1.25 mg/mL (2.45 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 12.5 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. View More
Solubility in Formulation 3: ≥ 1.25 mg/mL (2.45 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9627 mL | 9.8135 mL | 19.6271 mL | |
| 5 mM | 0.3925 mL | 1.9627 mL | 3.9254 mL | |
| 10 mM | 0.1963 mL | 0.9814 mL | 1.9627 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.
Link: https://clinicaltrials.gov/ct2/show/NCT05055258
Conditions:Angioedema, Hereditary, Types I and IILink: https://clinicaltrials.gov/ct2/show/NCT05178355
Conditions:Hereditary AngioedemaProducts are for research use only; We do not sell to patients
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