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 to cancer cells[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 [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 (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.