| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Targets |
FEN1-IN-4 targets human flap endonuclease-1 (hFEN1), a key enzyme in DNA replication and repair that cleaves RNA-DNA flap structures. By inhibiting hFEN1, the compound disrupts DNA replication and repair, inducing double-strand breaks (DSBs) and senescence. FEN1 inhibition selectively impairs proliferation of colon cancer cells deficient in Cdc4 and Mre11a.
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| ln Vitro |
Because of its role in LP-BER, FEN1 has also emerged as a potential chemosensitizing target because it is essential for repairing methyl mesylate-induced alkylation damage and its knockdown or inhibition increases glutinogenesis. Sensitivity to temozolomide in blastoma and colorectal cancer cell lines[1]. FEN1 inhibition selectively impairs proliferation of colon cancer cells lacking Cdc4 and Mre11a, both of which are frequently mutated in colorectal cancer.
In vitro, FEN1-IN-4 is a potent inhibitor of hFEN1 with an IC50 of 30 nM for hFEN1-336Δ. It abrogates mtDNA fragmentation and cytosolic Ox-mtDNA and mtDNA release. FEN1 inhibition selectively impairs proliferation of colon cancer cells deficient in Cdc4 and Mre11a. The compound's activity is assessed in enzyme inhibition and cell proliferation assays. |
| ln Vivo |
In vivo, FEN1-IN-4 inhibits alum-induced NLRP3 inflammasome-dependent IL-1β production and reduces neutrophil and monocyte infiltration. Its ability to inhibit FEN1 and modulate inflammasome activation suggests potential applications in inflammatory diseases and cancer. Further in vivo studies are needed to evaluate its therapeutic potential.
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| Enzyme Assay |
The in vitro enzyme inhibition assay for FEN1-IN-4 measures its ability to inhibit hFEN1 enzymatic activity. The assay is performed using purified hFEN1 enzyme and a fluorescent or radiolabeled flap substrate. The compound's ability to inhibit the cleavage of the flap substrate is measured, and IC50 values are calculated. Selectivity is assessed by testing against other nucleases.
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| Cell Assay |
In vitro cellular studies are conducted using colon cancer cell lines. Cells are treated with FEN1-IN-4 at various concentrations. Cell viability is assessed using MTT or CellTiter-Glo assays. DNA damage is assessed by measuring γH2AX foci formation or comet assays. Cell cycle analysis is performed by flow cytometry. Inflammasome activation is assessed by measuring IL-1β and IL-18 secretion in macrophage cultures.
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| Animal Protocol |
In vivo animal experiments are performed in models of inflammation or cancer. Animals are administered FEN1-IN-4 via various routes at different doses. Inflammatory markers such as IL-1β are measured in serum or tissues. Neutrophil and monocyte infiltration is assessed by immunohistochemistry or flow cytometry. Tumor growth inhibition is measured in xenograft models.
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| ADME/Pharmacokinetics |
FEN1-IN-4 has a molecular formula of C12H12N2O3 and a molecular weight of 232.24 g/mol. It is also known as FEN1 Inhibitor C2 and JUN93587. For storage, it should be kept at -20°C, protected from light and moisture. The compound is supplied with high purity for research purposes. It is a selective inhibitor of human flap endonuclease-1 (hFEN1).
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| Toxicity/Toxicokinetics |
As a research chemical with potent biological activity, FEN1-IN-4 is not intended for human use. Its toxicological profile is not fully characterized. Standard laboratory safety precautions should be followed when handling it. Its effects are related to its mechanism as a FEN1 inhibitor, which could have significant effects on DNA repair and inflammation.
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| References | |
| Additional Infomation |
FEN1-IN-4 is also known as FEN1 Inhibitor C2, JUN93587, and Compound 2. It is a human flap endonuclease-1 (hFEN1) inhibitor with an IC50 of 30 nM. FEN1-IN-4 abrogates mtDNA fragmentation and inhibits NLRP3 inflammasome-dependent IL-1β production. It is used in research on DNA repair, cancer, and inflammation.
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| Molecular Formula |
C12H12N2O3
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| Molecular Weight |
232.2353
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| Exact Mass |
232.084
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| CAS # |
1995893-58-7
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| PubChem CID |
121231495
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| Appearance |
Light yellow to yellow 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 |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
17
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| Complexity |
354
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1N(C(C2=C([H])C([H])=C([H])C([H])=C2N1C([H])([H])C1([H])C([H])([H])C1([H])[H])=O)O[H]
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| InChi Key |
JAFLWTUYSKADJS-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C12H12N2O3/c15-11-9-3-1-2-4-10(9)13(7-8-5-6-8)12(16)14(11)17/h1-4,8,17H,5-7H2
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| Chemical Name |
1-(cyclopropylmethyl)-3-hydroxyquinazoline-2,4-dione
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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 : ~125 mg/mL (~538.24 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.96 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 20.8 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: ≥ 2.08 mg/mL (8.96 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 20.8 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: ≥ 2.08 mg/mL (8.96 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 | 4.3059 mL | 21.5295 mL | 43.0589 mL | |
| 5 mM | 0.8612 mL | 4.3059 mL | 8.6118 mL | |
| 10 mM | 0.4306 mL | 2.1529 mL | 4.3059 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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