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| 5mg |
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| Targets |
FK 706 targets human neutrophil elastase, a serine protease involved in inflammation and tissue degradation. It is a slow-binding and competitive inhibitor with an IC50 of 83 nM and a Ki of 4.2 nM. FK 706 also inhibits mouse neutrophil elastase (IC50=22 nM) and porcine pancreatic elastase (IC50=100 nM), and shows activity against other serine proteases.
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| ln Vitro |
FK706 has an IC50 value of 230 nM and efficiently inhibits the hydrolysis of bovine cervical ligament elastin (final concentration 2 mg/mL) by human neutrophil elastase (final concentration 4 μg/mL)[1]. FK706 suppresses inflammatory chemokine release, mRNA expression of MCP-1 and IL-8, and NF-κB activation. FK706 may inhibit NF-κB activation in human lung fibroblasts directly, which would stop inflammatory chemokines from being expressed when lung inflammation brought on by cigarette smoke [2].
In vitro, FK 706 potently inhibits human neutrophil elastase with an IC50 of 83 nM and a Ki of 4.2 nM. It also inhibits mouse neutrophil elastase (IC50=22 nM) and porcine pancreatic elastase (IC50=100 nM). FK 706 demonstrates activity against other serine proteases including human trypsin, human pancreatic α-chymotrypsin, and human leukocyte cathepsin G. The compound blocks elastin degradation in vitro. |
| ln Vivo |
In a dose-dependent manner, FK706 (10-100 mg/kg; subcutaneous injection; duration 1-6 hours; male C57BL mice) therapy effectively reduces the edema (20 μg/paw) generated in mouse paws by human neutrophil elastase [1].
In vivo, FK 706 demonstrates strong anti-inflammatory effects by blocking elastin degradation, suppressing IL-8 and MCP-1 expression, and inhibiting NF-κB activation. Subcutaneous administration of FK 706 has been studied in animal models. The compound's inhibition of neutrophil elastase reduces tissue damage and inflammation in vivo. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for FK 706 involves measuring its inhibitory effect on human neutrophil elastase activity. Recombinant or purified human neutrophil elastase is incubated with varying concentrations of FK 706 and a fluorogenic or chromogenic substrate. Enzymatic activity is measured by monitoring substrate cleavage, and the IC50 and Ki are calculated from dose-response curves. FK 706 shows an IC50 of 83 nM and a Ki of 4.2 nM.
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| Cell Assay |
In vitro cellular assays for FK 706 involve treating cultured human neutrophils or other inflammatory cells with varying concentrations of the compound. Elastase activity in cell lysates or supernatants is measured using fluorogenic substrates. Cytokine levels (e.g., IL-8, MCP-1) are measured by ELISA. NF-κB activation is assessed using reporter gene assays or by measuring NF-κB nuclear translocation. FK 706 suppresses IL-8 and MCP-1 expression and inhibits NF-κB activation.
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| Animal Protocol |
Animal/Disease Models: Male C57BL mice (6 weeks old) were injected with human neutrophil elastase [1]
Doses: 10 mg/kg, 32 mg/kg, 100 mg/kg Route of Administration: subcutaneous injection; 1 hour, 2 hrs (hrs (hours)), 4 hrs (hrs (hours)), and 6 hrs (hrs (hours)) Experimental Results: Dramatically inhibited human neutrophil elastase-induced mouse paw edema in a dose-dependent manner. In vivo animal experiments for FK 706 typically use rodent models of inflammation, such as carrageenan-induced paw edema or LPS-induced lung inflammation. FK 706 is administered subcutaneously at various doses. Inflammatory markers (e.g., IL-8, MCP-1, myeloperoxidase) are measured in tissue or serum. Elastin degradation is assessed by measuring desmosine levels. FK 706 reduces inflammation by blocking elastin degradation and inhibiting NF-κB activation. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of FK 706 have not been extensively characterized in publicly available literature. The compound has a molecular weight of 592.54 (C26H32F3N4NaO7). As a small molecule serine protease inhibitor, FK 706 is expected to be administered parenterally (e.g., subcutaneous). Specific PK parameters including half-life, bioavailability, and metabolic pathways are not well documented.
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| Toxicity/Toxicokinetics |
Toxicological (toxicology) data for FK 706 are limited in publicly available sources. As a neutrophil elastase inhibitor, FK 706 may affect immune function and host defense against infection. The compound's anti-inflammatory effects may also impact normal tissue repair processes. Complete toxicology studies including acute, repeated-dose, and genotoxicity assessments would be required for therapeutic development.
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| References | |
| Additional Infomation |
See also: FK 706 (Notes have been moved to).
FK 706 (CAS#: 144055-55-0) is a potent, slow-binding, competitive inhibitor of human neutrophil elastase with an IC50 of 83 nM and a Ki of 4.2 nM. It also inhibits mouse and porcine elastases and demonstrates strong anti-inflammatory effects by blocking elastin degradation, suppressing IL-8 and MCP-1, and inhibiting NF-κB activation. FK 706 is not approved for clinical use and remains a research compound. |
| Molecular Formula |
C26H32F3N4NAO7
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|---|---|
| Molecular Weight |
592.539868354797
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| Exact Mass |
592.212
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| CAS # |
144055-55-0
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| PubChem CID |
23690296
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
11
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| Heavy Atom Count |
41
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| Complexity |
985
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| Defined Atom Stereocenter Count |
2
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| SMILES |
[Na+].FC(C(C(C(C)C)NC([C@@H]1CCCN1C([C@H](C(C)C)NC(C1C=CC(C(NCC(=O)[O-])=O)=CC=1)=O)=O)=O)=O)(F)F
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| InChi Key |
DNTYCMNNMGACPR-JSAITXCESA-M
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| InChi Code |
InChI=1S/C26H33F3N4O7.Na/c1-13(2)19(21(36)26(27,28)29)31-24(39)17-6-5-11-33(17)25(40)20(14(3)4)32-23(38)16-9-7-15(8-10-16)22(37)30-12-18(34)35;/h7-10,13-14,17,19-20H,5-6,11-12H2,1-4H3,(H,30,37)(H,31,39)(H,32,38)(H,34,35);/q;+1/p-1/t17-,19?,20-;/m0./s1
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| Chemical Name |
sodium;2-[[4-[[(2S)-3-methyl-1-oxo-1-[(2S)-2-[(1,1,1-trifluoro-4-methyl-2-oxopentan-3-yl)carbamoyl]pyrrolidin-1-yl]butan-2-yl]carbamoyl]benzoyl]amino]acetate
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| Synonyms |
FK706; FK-706; FK 706
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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: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~115 mg/mL (~194.08 mM)
H2O : ≥ 100 mg/mL (~168.76 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (8.44 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 50.0 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: ≥ 5 mg/mL (8.44 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 50.0 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. View More
Solubility in Formulation 3: ≥ 5 mg/mL (8.44 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 | 1.6876 mL | 8.4382 mL | 16.8765 mL | |
| 5 mM | 0.3375 mL | 1.6876 mL | 3.3753 mL | |
| 10 mM | 0.1688 mL | 0.8438 mL | 1.6876 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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