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.
IC50&Target
TBK1
2 nM (IC50, low ATP)
TBK1
30 nM (IC50, high ATP)
IKKε
2 nM (IC50)
体外研究
BAY-985 inhibits FLT3, RSK4, DRAK1, and ULK1 with IC50s of 123, 276, 311, and 7930 nM, respectively.
BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 (IRF3) with an IC50 of 74 nM.
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.
Cell Proliferation Assay
Cell Line:
ACHN and SK-MEL-2 cell lines
Concentration:
Incubation Time:
96 hours
Result:
Inhibited proliferation in SK-MEL2 and ACHN cells with IC50s of 900 and 7260 nM, respectively.
体内研究
BAY-985 (200 mg/kg; p.o.; b.i.d.; 111 days) results in weak antitumor efficacy.
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).
Animal Model:
Female NMRI nude mice bearing SK-MEL-2 human melanoma xenograft model
Dosage:
200 mg/kg
Administration:
Applied p.o.; twice daily (b.i.d.) continuously 111 days
Result:
Treatment resulted in weak antitumor efficacy with a T/Ctumor weight ratio of 0.6.
The treatment was well tolerated, with a maximum body weight loss of less than 10%.
分子式
C27H30F3N9O
分子量
553.58
CAS号
2409479-29-2
运输条件
Room temperature in continental US; may vary elsewhere.