Powder: -20°C for 3 years | In solvent: -80°C for 1 year
BI-D1870 是一种可渗透细胞和透过血脑屏障的的 ATP 竞争性核糖体 S6 激酶抑制剂,抑制 RSK1、RSK2、RSK3和 RSK4 的 IC50值分别为 31 nM、24 nM、18 nM 和15 nM。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 389 | 现货 | ||
2 mg | ¥ 563 | 现货 | ||
5 mg | ¥ 955 | 现货 | ||
10 mg | ¥ 1,530 | 现货 | ||
25 mg | ¥ 2,520 | 现货 | ||
50 mg | ¥ 3,990 | 现货 | ||
100 mg | ¥ 5,430 | 现货 | ||
500 mg | ¥ 11,300 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 822 | 现货 |
产品描述 | BI-D1870 is a cell-permeable, ATP-competitive inhibitor of ribosomal S6 kinases (RSKs; IC50s: 31/24/18/15 nM for RSK1/2/3/4). |
靶点活性 | RSK3:18 nM (cell free), RSK2:24 nM (cell free), RSK1:31 nM (cell free), RSK4:15 nM (cell free) |
体外活性 | BI-D1870 is cell permeant and prevents the RSK-mediated phorbol ester- and EGF (epidermal growth factor)-induced phosphorylation of GSK-3β and LKB1 in HEK 293 cells and Rat-2 cells. In contrast, BI-D1870 does not affect the agonist-triggered phosphorylation of substrates for six other AGC kinases. Moreover, BI-D1870 does not suppress the phorbol ester- or EGF-induced phosphorylation of CREB (cAMP-response-element-binding protein) [1]. In LN-229 cells, 1 μM BI-D1870 did not affect the phosphorylation of p70S6K, and rpS6 was scarcely reduced. However, 10 μM BI-D1870 strongly induced p70S6K activation after 90 min of incubation. In LN-18 cells, BI-D1870 at 10 μM stimulated the phosphorylation of rpS6 and p70S6K, displaying a peak at 90 min [2]. BI-D1870 exhibited a dose-responsive antiproliferative effect on OSCC cells with relative sparing of normal human oral keratinocytes. The compound inhibited the downstream RSK target YB-1 and caused apoptosis. In addition, BI-D1870 also induced G2/M arrest by modulating the expression of p21 and other cell cycle regulators. Other newly discovered anticancer attributes of BI-D1870 included the generation of reactive oxygen species and increases in endoplasmic reticulum stress and autophagy [3]. |
体内活性 | BI-D1870 (0.5 mg/kg) administration protected mice from experimental autoimmune encephalomyelitis (EAE) by reducing the infiltration of TH1 and TH17 cells into the CNS and decreasing mRNA levels of Ccr6 in TH17 cells [4]. |
激酶实验 | Purified His6–RSK1, His6–RSK2 or GST–RSK21–389:S381E (1–2 units/ml) were assayed for 10 min at 30 °C in a 50 μl assay mixture in Buffer A containing 30 μM substrate peptide (KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK), 10 mM magnesium acetate and 100 μM of [γ-32P]ATP. Reactions were terminated and analyzed as described previously. The amount of enzyme that catalyzed the phosphorylation of 1 nmol of substrate peptide in 1 min was termed one unit. In order to assay RSK and MSK1 in HEK-293 or Rat-2 cell lysates, these kinases were immunoprecipitated from the cell lysates (0.1 mg of lysate protein for RSK and 0.3 mg for MSK1) and assayed as described previously, except that for RSK assays the immunoprecipitates were washed twice with Buffer A containing 1 mM ATP and twice with Buffer A prior to the assay, as a precaution to ensure dissociation of BI-D1870 from the RSK isoforms [1]. |
细胞实验 | The rat embryo fibroblast cell line, Rat-2 cells were cultured on 10 cm-diameter dishes in Dulbecco's Modified Eagle's medium supplemented with 10% (v/v) FBS. HEK-293 cells were cultured on 10 cm-diameter dishes in Dulbecco's Modified Eagle's medium supplemented with 10% FBS and 1×antimycotic/antibiotic solution. Prior to stimulation, cells were cultured in the absence of serum for 16 h. Inhibitors were dissolved in DMSO at a 1000-fold higher concentration than they were used at. These inhibitors, or the equivalent volume of DMSO as a control, were added to the tissue culture medium 30 min prior to stimulation unless indicated otherwise. The final concentration of DMSO in the culture medium was 0.1% and had no effect on agonist-induced activation or phosphorylation of any of the substrates examined. The cells were stimulated with the indicated agonists and lysed in 1 ml of ice-cold Lysis Buffer and centrifuged at 16000 g at 4 °C for 5 min. The supernatants were frozen in liquid nitrogen and stored at ?80 °C until use. Protein concentrations were determined using the Bradford method with BSA as the standard [1]. |
动物实验 | Myelin oligodendrocyte glycoprotein (MOG) peptide 35–55. (MEVGWYRSPFSRVVHLYRNGK) (BEX) was used to induce EAE in C57/BL6J mice. Mice were injecteds.c. with 200 g of MOG peptide in100 L of PBS emulsified in 100 L complete Freund's adjuvant (CFA) that was further supplemented with five mg mL?1 Mycobacterium tuberculosis (H37Ra). In addition, 500 ng pertussis toxin was injected i.p. on days zero and two. The RSK inhibitor (BI-D1870; 0.5 mg kg?1) was injected i.p. into mice two days after immunization with MOG peptide, and injection was repeated every other day for 11 days. Mice that received only dimethyl sulfoxide (DMSO) solution were used as controls. Paralysis was evaluated according to the following scale: zero, no disease; one, tail limpness; two, hind limb weakness; three, hind limb paralysis; four, forelimb weakness; five, quadriplegia; six, death. For histological analysis, CNS samples were fixed with 4% paraformaldehyde and sliced at 4 m, and then hematoxylin & eosin (H & E) staining was performed [4]. |
化合物与蛋白结合的复合物 |
Crystal Structure of Human Vaccinia-related kinase 2 (VRK-2) bound to BI-D1870 |
分子量 | 391.42 |
分子式 | C19H23F2N5O2 |
CAS No. | 501437-28-1 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
H2O: < 1 mg/mL (insoluble or slightly soluble)
DMSO: 72 mg/mL (183.9 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.5548 mL | 12.774 mL | 25.548 mL | 63.87 mL |
5 mM | 0.511 mL | 2.5548 mL | 5.1096 mL | 12.774 mL | |
10 mM | 0.2555 mL | 1.2774 mL | 2.5548 mL | 6.387 mL | |
20 mM | 0.1277 mL | 0.6387 mL | 1.2774 mL | 3.1935 mL | |
50 mM | 0.0511 mL | 0.2555 mL | 0.511 mL | 1.2774 mL | |
100 mM | 0.0255 mL | 0.1277 mL | 0.2555 mL | 0.6387 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
BI-D1870 501437-28-1 Autophagy MAPK PI3K/Akt/mTOR signaling S6 Kinase BI-D 1870 inhibit Ribosomal S6 Kinase (RSK) S6K Inhibitor BI-D-1870 BI D1870 BID1870 inhibitor