| 名稱 | R406 free base |
| 描述 | R406 free base (R406 (free base)) is a potent Syk inhibitor. |
| 細(xì)胞實(shí)驗(yàn) | DLBCL cell lines are treated with serial dilutions of R406 (0.3, 0.6, 1.25, 2.5, or 5 μM) for 72 or 96 hours. Thereafter, cellular proliferation is determined by MTT assay, and cell apoptosis is assessed by using annexin V–FITC/propidium iodide (PI) staining. For the determination of caspase 9, 8, and 3, cells are lysed, size-fractionated by polyacrylamide gel electrophoresis (PAGE), and immunoblotted. (Only for Reference) |
| 激酶實(shí)驗(yàn) | In-vitro Fluorescence Polarization Kinase Assays: R406 is serially diluted in DMSO and then diluted to 1% DMSO in kinase buffer (20 mM HEPES, pH 7.4, 5 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.1 mg/mL acetylated BGG). ATP and substrate in kinase buffer are added at room temperature, resulting in a final DMSO concentration on 0.2%. The kinase reactions are performed in a final volume of 20 μL containing 5 μM HS1 peptide substrate and 4 μM ATP and started by addition of 0.125 ng of Syk in kinase buffer. The reaction is allowed to proceed for 40 minutes at room temperature. The reaction is stopped by the addition of 20 μL of PTK quench mix containing EDTA/anti-phosphotyrosine antibody (1X final)/fluorescent phosphopeptide tracer (0.5X final) diluted in FP Dilution Buffer. The plate is incubated for 30 minutes in the dark at room temperature and then read on a Polarion fluorescence polarization plate reader. Data are converted to amount of phosphopeptide present using a calibration curve generated by competition with the phosphopeptide competitor provided in the Tyrosine Kinase Assay Kit. For IC50 determination, R406 is tested at eleven concentrations in duplicate and curve-fitting is performed by non-linear regression analysis using Prism GraphPad Software. |
| 體外活性 | R406口服給藥患免疫復(fù)合物導(dǎo)致炎癥反應(yīng)的小鼠,明顯抑制皮膚反向被動(dòng)Arthus反應(yīng),1 mg/kg和5 mg/kg R406處理,與對(duì)照組相比則抑制分別為72%和86%.用10 mg/kg R406處理用膠原抗體處理的小鼠,明顯減少炎癥和腫脹,將進(jìn)行性關(guān)節(jié)炎降低至較低水平,且延遲K/BxN血清轉(zhuǎn)移小鼠模型發(fā)病,降低臨床關(guān)節(jié)炎達(dá)50%. |
| 體內(nèi)活性 | 1 μM或4 μM R406處理DLBCL細(xì)胞系,誘導(dǎo)caspases 9和3激活,而不激活caspase 8,導(dǎo)致大部分細(xì)胞凋亡。R406在不同細(xì)胞中,選擇性抑制Syk依賴的信號(hào)通路,EC50為33 nM到171 nM,比作用于Syk非依賴性通路效果好很多。R406抑制大型彌漫大B細(xì)胞淋巴瘤（DLBCL）細(xì)胞系的細(xì)胞增殖,EC50值范圍為0.8 μM至8.1 μM。R406的預(yù)處理在B細(xì)胞受體（BCR）交聯(lián)后完全阻斷SYK525/526的磷酸化和R406敏感的DLBCL中SYK依賴性磷酸化BLNK。R406處理24和48小時(shí)后,有效降低MMP-9 mRNA水平,比對(duì)照組分別降低2.8和4.3倍,并降低RL細(xì)胞侵襲能力。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 4.71 mg/mL (10 mM), Sonication is recommended.
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
|
| 關(guān)鍵字 | Inhibitor | FLT3 | Syk | Cluster of differentiation antigen 135 | R406 free base | inhibit | R-406 free base | CD135 | R406 | Fms like tyrosine kinase 3 | Apoptosis | Spleen tyrosine kinase | R 406 | R-406 |
| 相關(guān)產(chǎn)品 | Lidocaine hydrochloride | Metronidazole | 5-Fluorouracil | Stavudine | Tributyrin | Dextran sulfate sodium salt (MW 4500-5500) | Myricetin | Sorafenib | L-Ascorbic acid | Acetylcysteine | Sodium 4-phenylbutyrate | Kaempferol |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 血管生成庫(kù) | 經(jīng)典已知活性庫(kù) | 抗癌化合物庫(kù) | 已知活性化合物庫(kù) | 激酶抑制劑庫(kù) | 含氟化合物庫(kù) | 細(xì)胞凋亡化合物庫(kù) | 口服活性化合物庫(kù) | 酪氨酸激酶分子庫(kù) |