| 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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| Other Sizes |
| Targets |
Flap endonuclease 1 (FEN1), a key enzyme in DNA damage repair, responsible for processing Okazaki fragments in DNA replication and DNA base excision repair.
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| ln Vitro |
The growth of colon cancer cells lacking Mre11a and Cdc4, both of which are often mutated in colorectal cancer, is selectively impaired by FEN1 suppression. Due to its involvement in LP-BER, FEN1 has also become a promising target for chemosensitization. FEN1 is essential for healing alkylation damage caused by methyl mesylate, and its suppression or knockdown promotes glioblastoma. The sensitivity of colorectal cancer cell lines and temozolomide to each other [1].
In vitro, FEN1 inhibition by FEN1-IN-3 selectively impairs colon cancer cell proliferation in Cdc4 and Mre11a deficiencies, both common in colorectal cancers. FEN1 is a potential chemosensitizer, critical for repairing methyl methanesulfonate-induced alkylation damage. Knockdown or inhibition of FEN1 increases temozolomide sensitivity in glioblastoma and colorectal cancer cells. |
| ln Vivo |
Due to limited in vivo data for this specific compound, general FEN1 inhibition reduces tumor growth in xenograft models by impairing DNA repair, leading to enhanced sensitivity to DNA-damaging agents like temozolomide, suggesting a role as a chemosensitizer in combination therapies.
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| Enzyme Assay |
Binding affinity for FEN1 is assessed via ELISA or surface plasmon resonance (SPR). Recombinant human FEN1 protein is immobilized, and serially diluted compound is added. Binding is detected with a labeled anti-FEN1 antibody or directly by SPR, and the EC50 is calculated from the dose-response curve.
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| Cell Assay |
For in vitro assays, colon cancer cell lines (e.g., HCT116) with Cdc4 or Mre11a deficiencies are treated with serially diluted FEN1-IN-3 (0.1-100 uM) for 72 hours. Cell proliferation is measured using an MTT or CellTiter-Glo assay. FEN1 inhibition is also evaluated using a cellular FEN1 cleavage assay, where cells are lysed after treatment and incubated with a fluorescent flap substrate.
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| Animal Protocol |
In a mouse xenograft model, immunocompromised mice are injected subcutaneously with Cdc4- or Mre11a-deficient colon cancer cells. When tumors reach ~100-200 mm3, FEN1-IN-3 is administered orally or intraperitoneally at 5-50 mg/kg daily. Tumor volume is measured with calipers, and tissues are harvested for FEN1 activity analysis via cleavage assay.
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| ADME/Pharmacokinetics |
FEN1-IN-3 has a molecular weight of 284.27 g/mol and a formula of C15H12N2O4. It is DMSO-soluble (50 mg/mL). Detailed in vivo PK parameters (e.g., half-life, Cmax, oral bioavailability) are not fully published but typical for small molecule FEN1 inhibitors, with moderate oral bioavailability and a short plasma half-life.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data specific to FEN1-IN-3 is limited. As a small molecule inhibitor of a DNA repair enzyme, toxicity may include myelosuppression or gastrointestinal effects, consistent with other DNA repair inhibitors. No severe toxicities have been reported at efficacious doses in research models.
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| References | |
| Additional Infomation |
FEN1-IN-3 is a research chemical not yet approved for clinical use. It is extracted from patent literature and is provided for laboratory research purposes only. It is used to study the role of FEN1 in DNA repair, replication stress, and as a potential target for chemosensitization in colorectal and other cancers.
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| Molecular Formula |
C15H12N2O4
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|---|---|
| Molecular Weight |
284.266783714294
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| Exact Mass |
284.079
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| CAS # |
2109805-87-8
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| PubChem CID |
132585224
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
1.8
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
21
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| Complexity |
420
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ON1C(C2C=CC=CC=2N(C1=O)C1C=CC(=CC=1)OC)=O
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| InChi Key |
BBJIIPZSHQTBLW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H12N2O4/c1-21-11-8-6-10(7-9-11)16-13-5-3-2-4-12(13)14(18)17(20)15(16)19/h2-9,20H,1H3
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| Chemical Name |
3-hydroxy-1-(4-methoxyphenyl)quinazoline-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: 250 mg/mL (879.45 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.32 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 (7.32 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 (7.32 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 | 3.5178 mL | 17.5889 mL | 35.1778 mL | |
| 5 mM | 0.7036 mL | 3.5178 mL | 7.0356 mL | |
| 10 mM | 0.3518 mL | 1.7589 mL | 3.5178 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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