| 名稱 | GW 5074 |
| 描述 | GW 5074 (Raf1 Kinase Inhibitor I)(IC50=9 nM) is an effective and specific c-Raf inhibitor. It has no effect on the activities of JNK1/2/3, MEK1, MKK6/7, CDK1/2, c-Src, p38 MAP, VEGFR2 or c-Fms. |
| 細(xì)胞實(shí)驗(yàn) | HCA is diluted from 100-fold concentrated solutions that are adjusted to pH 7.5. To evaluate the effects of GW5074 on HCA-induced cytotoxicity, GW5074 is added at the time cortical neurons are exposed to HCA. Viability is assessed 24 h later.(Only for Reference) |
| 激酶實(shí)驗(yàn) | Affinity determination: In general, in vitro kinase assays are performed using purified kinase and synthetic substrates under standard conditions using the Kinase Profiling service of Upstate Biotechnology. Briefly, for each assay 5–10 mU of purified kinase is used. For GSK3β, cdk1, cdk2, cdk3, cdk5, the kinase is incubated with 1 μM GW5074 in a buffer containing 8 mM MOPS, pH 7.2, 0.2 mM EDTA, 10 mM magnesium acetate and [c- 33P-ATP] for 40 min at room temperature. Kinase activity is quantified by measuring 33P incorporation by spotting an aliquot on P30 filters, washing in 50 mM phosphoric acid and scintillation counting. The buffer composition for c-Raf, JNK1, JNK2, JNK3, MEK1, MKK6, MKK7 is 50 mM Tris pH 7.5, 0.1 mM EGTA, 10 mM magnesium acetate and [c- 33P-ATP]. The peptide substrates used are as follows: For c-Raf, 0.66 mg/mL MBP; for cdks, 0.1 mg/mL histone H1; for JNKs, 3 μM ATF2; for MEK1, 1 μM MAPK2; for MKK6, 1 μM of SAPK2a and for MKK7, 2 μM JNK1α. |
| 體外活性 | GW5074是一種強(qiáng)效且特異性的c-Raf抑制劑，其IC50為9 nM，但對MKK6、MKK7、p38 MAP激酶及cdks無影響。然而，在體外條件下，神經(jīng)細(xì)胞培養(yǎng)處理中GW5074可促進(jìn)c-Raf及B-Raf上激活修飾的積累。GW5074抑制LK引起的小腦顆粒神經(jīng)元凋亡，并非依賴MEK-ERK。GW5074能延遲Akt活性下調(diào)，但通過Akt獨(dú)立機(jī)制抑制凋亡。此外，GW5074對Ras、核因子-κB及c-jun有影響，并抑制由神經(jīng)毒素引起的顆粒細(xì)胞及其他神經(jīng)類型的細(xì)胞死亡。[1] |
| 體內(nèi)活性 | GW5074在亨廷頓病的活體實(shí)驗(yàn)?zāi)Ｐ椭斜憩F(xiàn)出保護(hù)作用。GW5074（5 mg/Kg）完全阻止了3-NP在小鼠中引發(fā)的廣泛雙側(cè)紋狀體損傷。[1] GW5074徹底消除了慢性嗎啡在穩(wěn)定表達(dá)人μ-阿片受體的CHO細(xì)胞中引起的AC超激活I(lǐng)。[2] 同時，GW5074還抑制了側(cè)流煙霧引起的小鼠氣道高反應(yīng)性。[3] |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 96 mg/mL (184.3 mM)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
H2O : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | GW 5074 | GW-5074 | inhibit | Raf | Apoptosis | Inhibitor | Raf kinases |
| 相關(guān)產(chǎn)品 | L-Glutamic acid | Metronidazole | 5-Fluorouracil | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Tributyrin | Myricetin | Sorafenib | L-Ascorbic acid | Acetylcysteine | Salicylic acid | Sodium 4-phenylbutyrate |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 抗癌化合物庫 | 已知活性化合物庫 | 激酶抑制劑庫 | 細(xì)胞凋亡化合物庫 | HIF-1化合物庫 | NO PAINS 化合物庫 | 抗肥胖化合物庫 | 疼痛相關(guān)化合物庫 |