产品说明书
SCH772984
 |
同义名 : | - |
| CAS号 : | 942183-80-4 | |
| 货号 : | A378792 | |
| 分子式 : | C33H33N9O2 | |
| 纯度 : | 99%+ | |
| 分子量 : | 587.674 | |
| MDL号 : | MFCD28144700 | |
| 存储条件： |
粉末 Sealed in dry,2-8°C 液体 -20°C:3-6个月-80°C:12个月 |
|
| 溶解度 : |
DMSO: 50 mg/mL(85.08 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO |
|
| 动物实验配方： |
IP 5% DMSO+water 0.4 mg/mL clear PO 0.5% CMC-Na 60 mg/mL suspension |
| 生物活性 | |||
|---|---|---|---|
| 靶点 |
|
||
| 描述 | ERK1/2 (extracellular-signal-regulated kinases) is only known substrates of the MEK1/2 as well as the essential node in RAS/RAF/MEK/ERK signaling cascade, which can be activated by catalyzing the phosphorylation on T202/Y204 through MEK1/2. SCH772984 is a specific and potent ERK1/2 inhibitor with IC50 value of 4 and 1 nM (measured by in vitro kinase activity). Exposure to SCH772984 at concentration ranging in 30-300nM dose-dependently inhibited the phosphorylation of ERK substrate, p90 ribosomal S6 kinase (RSK), on T359/S363 site, as well as caused the inhibition of phosphorylation of residues in the activation loop of ERK itself at the higher dose (>100 nM). This was further confirmed by comparison with the ATP-competitive ERK inhibitor, VTX-11e. Though both of this two inhibitor inhibited p-RSK at concentration ranging in 0.1-2 μM in BRAFV600E-mutant A375 melanoma cell line, only SCH772984 showed suppression on p-ERK. The cell growth assay studies showed that SCH772984 was efficacious on growth inhibition of RAS- or BRAF- mutant cancer cells, as well as in cells resistant to single-agent BRAF or MEK inhibitor tested. Consistent with this cellular results, intraperitoneal injection with SCH772984 at dose of 12.5, 25 and 50 mg/kg, twice daily for 14 days, efficiently suppressed tumor growth, with obvious p-ERK inhibition, in human LOX BRAF-mutant melanoma xenograft model, while suppression of MiaPaCa KRAS-mutant pancreatic tumor growth can be observed at dose of both 25 and 50 mg/kg in nude mice[1]. | ||
| 作用机制 | SCH772984 may inhibit ERK1/2 both through ATP-competition and inducing or stabilizing a conformational state in ERK that prevents activation by MEK.[1] | ||
| 细胞研究 | |||||
|---|---|---|---|---|---|
| 细胞系 | 浓度 | 检测类型 | 检测时间 | 活动说明 | 数据源 |
| 2P-ERK2 | Growth Inhibition Assay | IC50=0.24 nM | 25350931 | ||
| 5637 | Growth Inhibition Assay | IC50=610 nM | 23614898 | ||
| 769P | Growth Inhibition Assay | IC50=3000 nM | 23614898 | ||
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
|
1 mM 5 mM 10 mM |
1.70mL 0.34mL 0.17mL |
8.51mL 1.70mL 0.85mL |
17.02mL 3.40mL 1.70mL |
| 参考文献 |
|---|