KU55933 is an ATP-competitive, thioanthrene-pyranone-based inhibitor of ATM kinase with an IC50 of 13 nM and Ki of 2.2 nM and >100-fold selectivity over PI3K related kinases. [1] KU55933 inhibits cell proliferation by inducing G1 cell cycle arrest by downregulation of cyclin D1 synthesis in MDA-MB-453 breast cancer cells and PC-3 prostate cancer cells. [2] KU55933 inhibits insulin- and IGF1-stimulated Akt phosphorylation at both Ser473 and Thr308. [2] ATM cellular inhibition by KU55933 was demonstrated in additional phosphorylation targets, including p53 Ser15, H2AX Ser139, NBS1 Ser343, Chk1 Ser345, and SMC1 Ser966. [1]

KU55933 is being studied as a radiosensitizer, having been shown to sensitize HeLa cells to the effects of topoisomerase inhibitors, etoposide, doxorubicin, amsacrine, and camptothecin. [1] When in combination with rapamycin, KU55933 induces apoptosis and arrests any induced feedback activation of Akt. [2]