APE1 Inhibitor III

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[1].

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

IC50: 2 μM (APE1)[1]

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)[1]. 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[1]. 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)[1]. Cell Cytotoxicity Assay[1] 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[1]. Pharmacokinetic Parameters of APE1-IN-1 (compound 3) (IP; 30 mpk) in CD1 mice[1]. Plasma Brain t1/2 (h) 2.1 1 brain/plasma 21 Cmax (μM) 16 217 tmax (h) 0.25 0.25 CLogP 2.83 Animal Model: CD1 male mice (n = 3)[1] 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.

[1]. Rai G, et al. Synthesis, biological evaluation, and structure-activity relationships of a novel class of apurinic/apyrimidinic endonuclease 1 inhibitors. J Med Chem. 2012 Apr 12;55(7):3101-12.