BAY-985

BAY-985 is a highly potent, orally active and selective ATP-competitive dual inhibitor of TBK1 and IKKε with IC50s of 2/30 and 2 nM for TBK1 (low/high ATP) and IKKε, respectively. Antitumor efficacy[1].

BAY-985 inhibits FLT3, RSK4, DRAK1, and ULK1 with IC50s of 123, 276, 311, and 7930 nM, respectively[1].BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 (IRF3) with an IC50 of 74 nM[1].BAY-985 is active in cellular mechanistic assay and shows anti-proliferative activity in a few cancer cell lines with IC50s of 900 and 7260 nM for SK-MEL2 (NRAS and TP53 mutated) and ACHN (CDKN2A mutated) cells, respectively[1]. Cell Proliferation Assay[1] Cell Line: ACHN and SK-MEL-2 cell lines

BAY-985 (200 mg/kg; p.o.; b.i.d.; 111 days) results in weak antitumor efficacy[1].BAY-985 shows high clearance (CLb= 4.0 L/h/kg, ca. 95% hepatic extraction), large volume of distribution at steady state (Vss=2.9 L/kg) and a short terminal half-life (t1/2=0.79 h)[1]. Animal Model: Female NMRI nude mice bearing SK-MEL-2 human melanoma xenograft model[1]

[1]. Lefranc J, et al. Discovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor. J Med Chem. 2020 Jan 10.