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| Targets |
FN-439 TFA is a matrix metalloproteinase (MMP) inhibitor with selectivity for collagenase-1 (MMP-1). MMPs are zinc-dependent endopeptidases that degrade extracellular matrix components including collagen, gelatin, and proteoglycans. MMP-1 specifically cleaves interstitial collagens (types I, II, III). By inhibiting MMP-1, FN-439 blocks collagen degradation and may affect processes such as tumor invasion, angiogenesis, and inflammation.
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| ln Vitro |
In vitro, FN-439 TFA inhibits collagenase-1 (MMP-1) with an IC50 of 1 uM. It also inhibits granulocyte gelatinase (MMP-9) with an IC50 of 30 uM and skin fibroblast stromelysin (MMP-3) with an IC50 of 150 uM. It shows no inhibition of thermolysin or serine proteinases at tested concentrations, indicating selectivity. The compound reduces collagen degradation and may affect cancer cell invasion and inflammatory responses in cellular models.
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| ln Vivo |
In vivo, FN-439 TFA has been studied in animal models. In a rat periapical lesion model, the combination of FN-439 (collagenase inhibitor) and ofloxacin (antibacterial agent) improved healing of periapical lesions. FN-439 may reduce tissue destruction by inhibiting MMP-mediated collagen breakdown in inflammatory conditions. The compound may be utilized in cancer and inflammation research to study the role of MMP-1 in disease progression.
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| Enzyme Assay |
For cell-free enzyme assays, incubate purified human MMP-1 (collagenase-1) (1-10 nM) with increasing concentrations of FN-439 TFA (0.1-100 uM) in assay buffer (50 mM Tris-HCl, 150 mM NaCl, 5 mM CaCl2, 0.05% Brij-35, pH 7.5) for 10-30 minutes at 37degC. Add the fluorogenic substrate (e.g., DQ-collagen or Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH2). Measure fluorescence at excitation 328 nm, emission 393 nm. Determine IC50 by nonlinear regression. For broad MMP profiling, test against MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, and MMP-14 using similar protocols.
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| Cell Assay |
Culture human breast cancer cells (e.g., MDA-MB-231) or fibroblast cell lines in DMEM with 10% FBS. For invasion assays, coat Transwell inserts with Matrigel. Add serum-free medium containing FN-439 TFA (1-100 uM) to the upper chamber and medium with 10% FBS as chemoattractant to the lower chamber. Seed cells (1 × 10^5) in the upper chamber. Incubate for 24 hours at 37degC. Stain invaded cells with crystal violet and count under a microscope. Alternatively, use collagen gel contraction assays to assess collagen degradation. Add FN-439 TFA (1-100 uM) and measure the reduction in gel diameter over 24-72 hours. Assess cell viability by MTT to rule out cytotoxicity. For inflammation studies, culture macrophages (RAW 264.7) and treat with LPS (1 ug/mL) with or without FN-439 (1-100 uM). Measure MMP-1, MMP-9, and pro-inflammatory cytokine (TNF-alpha, IL-6) levels by ELISA.
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| Animal Protocol |
For in vivo efficacy studies, use the rat periapical lesion model: create periapical lesions by exposing rat mandibular first molars. Administer FN-439 TFA via local injection or systemic administration (e.g., oral or intraperitoneal) at doses of 1-10 mg/kg daily for 1-4 weeks. Co-administer ofloxacin (10 mg/kg) in some experiments. At sacrifice, harvest jaw tissues, fix, decalcify, section, and stain with H&E for histopathological assessment of lesion size and inflammatory cell infiltration. Evaluate bone resorption by TRAP staining. Alternatively, use a tumor xenograft model (e.g., MDA-MB-231 injected subcutaneously into nude mice). Administer FN-439 TFA (10 mg/kg i.p. daily) for 2-4 weeks. Monitor tumor volume by caliper measurement. Harvest tumors at endpoint for IHC analysis of MMP-1 expression and collagen content by picrosirius red staining. For metastasis models (e.g., tail vein injection of cancer cells), administer FN-439 TFA and quantitate lung metastasis by counting surface nodules after India ink staining.
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| ADME/Pharmacokinetics |
FN-439 TFA is a hydroxamic acid-based MMP inhibitor. The TFA salt form enhances water solubility (H2O: 250 mg/mL, ~413.51 mM). In vivo pharmacokinetic properties are not extensively documented. As a small molecule MMP inhibitor (MW 604.58), it is expected to have moderate oral bioavailability and tissue distribution. For in vivo studies, formulations include DMSO/Tween 80/saline (10:5:85) or DMSO/PEG300/Tween 80/saline (10:40:5:45). Storage: Powder at -80degC (2 years) or -20degC (1 year); in solvent at -80degC (6 months) or -20degC (1 month), sealed, away from moisture and light.
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| Toxicity/Toxicokinetics |
FN-439 TFA has a favorable safety profile in preclinical models at effective doses (1-10 mg/kg). In rat studies, no significant acute toxicity or adverse effects were reported. The compound is selective for MMP-1 over other proteases (>100-fold selectivity vs. serine proteinases). No genotoxicity or carcinogenicity data are publicly available. The TFA salt may cause mild irritation. Standard laboratory precautions (gloves, lab coat, safety glasses) should be used. Avoid inhalation of fine powder. Dispose of waste according to institutional guidelines.
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| References |
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| Additional Infomation |
FN-439 TFA is also known as FN439 TFA. The compound is a selective collagenase-1 (MMP-1) inhibitor with an IC50 of 1 uM, used in cancer and inflammation research. It is covered in patents and literature relating to matrix metalloproteinase inhibition. The sequence of FN-439 corresponds to the peptide 4-Abz-Gly-Pro-D-Leu-D-Ala-NHOH. The TFA salt form is used for enhanced solubility and stability. The compound is for research use only and not for diagnostic or therapeutic applications.
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| Molecular Formula |
C25H35F3N6O8
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| Molecular Weight |
604.58
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| Related CAS # |
FN-439;124168-73-6
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| Appearance |
White to off-white solid powder
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
H2O :~250 mg/mL (~413.51 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6540 mL | 8.2702 mL | 16.5404 mL | |
| 5 mM | 0.3308 mL | 1.6540 mL | 3.3081 mL | |
| 10 mM | 0.1654 mL | 0.8270 mL | 1.6540 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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