FEN1-IN-3 (Compound 4) is a human flap endonuclease-1 (hFEN1) inhibitor. FEN1-IN-3 stabilizes hFEN1 with EC50 of 6.8 μM.

Physicochemical Properties

Molecular Formula	C15H12N2O4
Molecular Weight	284.266783714294
Exact Mass	284.079
CAS #	2109805-87-8
PubChem CID	132585224
Appearance	Light yellow to yellow solid powder
LogP	1.8
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	2
Heavy Atom Count	21
Complexity	420
Defined Atom Stereocenter Count	0
SMILES	ON1C(C2C=CC=CC=2N(C1=O)C1C=CC(=CC=1)OC)=O
InChi Key	BBJIIPZSHQTBLW-UHFFFAOYSA-N
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
Chemical Name	3-hydroxy-1-(4-methoxyphenyl)quinazoline-2,4-dione
HS Tariff Code	2934.99.9001
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)

Biological Activity

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].

References

[1]. Cellularly Active N-hydroxyurea FEN1 Inhibitors Block Substrate Entry to the Active Site. Nat Chem Biol. 2016 Oct;12(10):815-21.

Solubility Data

Solubility (In Vitro)

DMSO: 250 mg/mL (879.45 mM)

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. 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. 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 corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

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.