APE1-IN-1

Research use only, not for human use.

APE1-IN-1 is a potent inhibitor of purine/pyrimidine endonuclease 1 (APE1) that crosses the blood-brain barrier, exhibits potential antitumor activity, and enhances the cytotoxicity of the alkylating agent [methyl methanesulfonate] on cancer cells.

APE1-IN-1 is a potent and blood-brain barrier (BBB) penetrant apurinic/apyrimidinic (AP) endonuclease 1 (APE1) inhibitor with an IC50 value of 2 μM. APE1-IN-1 can potentiate the cytotoxicity of the alkylating agents Methylmethane sulfonate and Temozolomide (HY-17364) to cancer cells.

APE1-IN-1 (compound 3) exhibits an IC50 of 2 μM in the qHTS assay and an IC50 of 12 μM in a radiotracer incision assay (RIA).APE1-IN-1 (0, 1, 3, 10, 30, or 100 μM; 15 min) inhibits HeLa whole cell extract AP site incision in a dose-dependent manner.APE1-IN-1 (5-30 μM; 24 h) exhibits cytotoxic activity against HeLa cells, and potentiates the activity of methyl methansulfonate and Temozolomide (HY-17364).Cell Cytotoxicity Assay Cell Line:HeLa cells Concentration:5-30 μM Incubation Time:24 h Result:Exhibited cytotoxic activity against HeLa cells with a 50% reduction in cell viability occurring at ~15 μM.Greatly potentiated the activity of methyl methansulfonate (0.4 mM) and Temozolomide (HY-17364) (1 mM) with optimal synergy occurring at ~5 μM and ~10 μM, respectively.

APE1-IN-1 (30 mpk; IP; single dosage) exhibits favorable pharmacokinetic property.Pharmacokinetic Parameters of APE1-IN-1 (compound 3) (IP; 30 mpk) in CD1 mice.Animal Model:CD1 male mice (n = 3)Dosage:30 mpk Administration:IP; single dosage Result:Showed lipophilic (CLogP = 2.8), crossed the BBB quite readily, giving rise to a B/P ratio of 21.

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Cell Cycle/DNA Damage

DNA/RNA Synthesis

DNA/RNA Synthesis

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524708-03-0

371.52

C19H21N3OS2

>98% (HPLC)

In Vitro:?DMSO : 22 mg/mL (59.22 mM; Ultrasonic (<80°C)

CC(C)N1CCc2c(C1)sc(NC(C)=O)c2-c1nc2ccccc2s1

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(-20℃)

With Ice Pack

≥ 2 years