BAY-8400 (BAY8400) is a highly potent, selective inhibitor of DNA-PK with biochemical IC50 of 81 nM, cellular IC50 of 69 nM (γH2AX in HT-144).
BAY-8400 showed good selectivity against PI3K and ATR, ATM and mTOR. In the KINOMEscan panel, >50% inhibition activity of BAY-8400 at 1 uM was measured only for three out of 365 kinases, including DNA-PK.
BAY-8400 demonstrates very potent antiproliferative activity against HT-29 cells in combination with the radiomimetic bleomycin (IC50=358 nM), while its antiproliferative activity in monotherapy was sevenfold lower (IC50=2540 nM).
Combination of PSMA-targeted thorium-227 conjugate BAY 2315497 treatment of human prostate tumor-bearing mice with BAY-8400 oral treatment increased antitumor efficacy,
