CAS:1449277-10-4GNE-495

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GNE-495 is a potent and selective MAP4K4 inhibitor with IC50 of 3.7 nM.

规格	价格	促销价格	库存

18817579266

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18817579266

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实验数据

技术信息

CAS号

1449277-10-4

储存条件

分子式

C22H20FN5O2

运输

蓝冰

分子量

405.42

别名

溶解度

DMSO	2.0 mg/mL (4.9 mM) warming
Water	Insoluble

动物实验配方

生物活性

描述The serine/threonine kinase MAP4K4 is a member of the Ste20p (sterile 20 protein) family. The role of MAP4K4 in immunity, inflammation, metabolic and cardiovascular disease has been recognized. Increasing evidence suggests that MAP4K4 plays an important role in cancer and MAP4K4 may represent a novel actionable cancer therapeutic target. GNE-495 is a potent and selective MAP4K4 inhibitor with an IC₅₀ of 3.7 nM. It shows the best balance of MAP4K4 inhibition, permeability, microsomal stability, and cellular potency. GNE-495 is administered intraperitoneally to neonatal mouse pups at high doses: 25 and 50 mg/kg. GNE-495 shows good in vivo profile in all species tested, with low clearances, moderate terminal half-lives, and reasonable oral exposure levels (F=37-47%). GNE-495 showed excellent potency and good PK and was used to demonstrate in vivo efficacy in a retinal angiogenesis model recapitulating effects that were observed in the inducible Map4k4 knockout mice.
作用机制The amide linker extending from the naphthyridine scaffold effectively replaces two of the water molecules and engages in a hydrogen-bonding interaction to the hinge Cys108 carbonyl. Overall, the binding pocket was completely occupied by the optimized ligand.