BAY-985

生物活性靶点体外研究体内研究 BAY-985 试剂级价格

BAY-985

CAS号:2409479-29-2
英文名:BAY-985
中文名:BAY-985
CBNumber:CB55839640
分子式:C27H30F3N9O
分子量:553.58
MOL File:2409479-29-2.mol

BAY-985化学性质

沸点 :753.3±70.0 °C(Predicted)
密度 :1.373±0.06 g/cm3(Predicted)
储存条件 :Store at -20°C
溶解度 :DMSO: 50 mg/mL (90.32 mM)
形态 :A solid
酸度系数(pKa) :10.06±0.10(Predicted)
颜色 :Light yellow to yellow

BAY-985性质、用途与生产工艺

生物活性 BAY-985是一种有效、高选择性的TBK1/IKKε抑制剂。 BAY-985对TBK1 (IC50 = 2 nM, low ATP assay; 30 nM, high ATP assay)和IKKε (IC50 = 2 nM)具有高效力，在机械性细胞phosphorylation of interferon regulatory factor 3(pIRF3)分析中也具有高效力(IC50 = 74 nM)，并且对SK-MEL-2细胞具有抗增殖作用(IC50 = 900 nM)。
靶点
Target Value
TBK1
(in low ATP assay) 2 nM
IKKε
(Cell-free assay) 2 nM
TBK1
(in high ATP assay) 30 nM
pIRF3
(Cell-free assay) 74 nM

体外研究

BAY-985 inhibits FLT3, RSK4, DRAK1, and ULK1 with IC ₅₀ s of 123, 276, 311, and 7930 nM, respectively.
BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 (IRF3) with an IC ₅₀ of 74 nM.
BAY-985 is active in cellular mechanistic assay and shows anti-proliferative activity in a few cancer cell lines with IC ₅₀ s 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 IC ₅₀ s 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 (CL _b = 4.0 L/h/kg, ca. 95% hepatic extraction), large volume of distribution at steady state (V _ss =2.9 L/kg) and a short terminal half-life (t _1/2 =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/C _{tumor weight} ratio of 0.6. The treatment was well tolerated, with a maximum body weight loss of less than 10%.