2409479-29-2

中文名称 BAY-985

英文名称 BAY-985

CAS 2409479-29-2

分子式 C27H30F3N9O

分子量 553.58

MOL 文件 2409479-29-2.mol

更新日期 2024/07/20 14:53:38

2409479-29-2 结构式

基本信息物理化学性质常见问题列表

基本信息

中文别名

化合物BAY-985

英文别名

BAY-985
1-Propanone, 1-[4-[(1R)-1-[2-[[6-[6-(dimethylamino)-4-pyrimidinyl]-1H-benzimidazol-2-yl]amino]-4-pyridinyl]ethyl]-1-piperazinyl]-3,3,3-trifluoro-

所属类别

生物化工：IκB/IKK 抑制剂

物理化学性质

沸点753.3±70.0 °C(Predicted)

密度1.373±0.06 g/cm3(Predicted)

储存条件-20°C储存

溶解度DMSO: 50 mg/mL (90.32 mM)

酸度系数(pKa)10.06±0.10(Predicted)

形态固体

颜色Light yellow to yellow

常见问题列表

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%.