BAY-985

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

BAY-985 是一种有效的、选择性的、口服活性的 ATP 竞争性 TBK1 和 IKKε 双重抑制剂（对于 TBK1（低/高 ATP）和 IKKε，IC50 为 2/30 和 2 nM），具有抗肿瘤功效。BAY-985 抑制 FLT3 、RSK4、DRAK1 和 ULK1（IC50：123、276、311 和 7930 nM）。 BAY-985 抑制干扰素调节因子 3 的细胞磷酸化（IRF3，IC50：74 nM）。

BAY-985 is a potent, selective, and orally active ATP-competitive dual inhibitor of TBK1 and IKKε (IC50s: 2/30 and 2 nM for TBK1 (low/high ATP) and IKKε) with antitumor efficacy.BAY-985 inhibits FLT3, RSK4, DRAK1, and ULK1 (IC50s: 123, 276, 311, and 7930 nM). BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 (IRF3, IC50: 74 nM). BAY-985 shows anti-proliferative activity in a few cancer cell lines (IC50s: 900 and 7260 nM for SK-MEL2 (NRAS and TP53 mutated) and ACHN (CDKN2A mutated) cells).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).

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.

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%.

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Immunology/Inflammation

IκB kinase (IKK)

TBK1|TBK1|IKKε

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2409479-29-2

553.58

C27H30F3N9O

>98% (HPLC)

DMSO:50 mg/mL (90.32 mM; Need ultrasonic)

C[C@@H](N1CCN(CC1)C(=O)CC(F)(F)F)c1ccnc(Nc2nc3ccc(cc3[nH]2)-c2cc(ncn2)N(C)C)c1

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(-20℃)

With Ice Pack

≥ 2 years