|8-氨基-N-(1-(环丙烷甲酰基)氮杂环丁烷-3-基)-2-(3-氟苯基)-1,7-萘啶-5-甲酰胺|CsnPharm

CAS No.: 1449277-10-4

GNE-495 Catalog No. CSN18723

Synonyms: GNE-495

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	数量

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

加入购物车大规格询价

加入收藏

产品咨询

400-920-2911

sales@csnpharm.cn

tech@csnpharm.cn

纯度 & 质量文件批次:

靶点选择性

生物活性

实验方案

技术信息

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^[1]. 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^[2]. 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^[2].
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.
参考文献

[1] Gao X, Gao C, Liu G, Hu J. MAP4K4: an emerging therapeutic target in cancer. Cell Biosci. 2016 Oct 28;6:56. doi: 10.1186/s13578-016-0121-7. PMID: 27800153; PMCID: PMC5084373.
[2] Ndubaku CO, Crawford TD, Chen H, Boggs JW, Drobnick J, Harris SF, Jesudason R, McNamara E, Nonomiya J, Sambrone A, Schmidt S, Smyczek T, Vitorino P, Wang L, Wu P, Yeung S, Chen J, Chen K, Ding CZ, Wang T, Xu Z, Gould SE, Murray LJ, Ye W. Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis. ACS Med Chem Lett. 2015 Jun 29;6(8):913-8. doi: 10.1021/acsmedchemlett.5b00174. PMID: 26288693; PMCID: PMC4538449.

实验方案

计算器摩尔计算器总药量计算器工作液计算器
储存液制备
- 1 mg
- 5 mg
- 10 mg
- 1 mM
- 2.4665 mL
- 12.3326 mL
- 24.6652 mL
- 5 mM
- 0.4933 mL
- 2.4665 mL
- 4.9330 mL
- 10 mM
- 0.2467 mL
- 1.2333 mL
- 2.4665 mL

技术信息

CAS号

1449277-10-4

储存条件

粉末: Keep in dark place,Sealed in dry,2-8°C

液体: -20°C:3-6 月 -80°C:12月

分子式

C22H20FN5O2

运输

蓝冰

分子量

405.42

别名

GNE-495

溶解度

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

动物实验配方

大规格询价

号为必填项

姓名: 邮箱: 手机号:

留言:

提交

GNE-495 Catalog No. CSN18723

靶点选择性

请登录您的专属账户

确认信息