Powder: -20°C for 3 years | In solvent: -80°C for 1 year
CP673451 是选择性的血小板源生长因子受体 (PDGFR) 抑制剂,能够抑制 PDGFRα (IC50:10 nM) 和 PDGFRβ (IC50:1 nM) 的活性。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 395 | 现货 | ||
2 mg | ¥ 568 | 现货 | ||
5 mg | ¥ 913 | 现货 | ||
10 mg | ¥ 1,660 | 现货 | ||
25 mg | ¥ 2,860 | 现货 | ||
50 mg | ¥ 4,230 | 现货 | ||
100 mg | ¥ 5,920 | 现货 | ||
500 mg | ¥ 12,300 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 983 | 现货 |
产品描述 | CP-673451 is a specific inhibitor of PDGFRα/β (IC50: 10/1 nM) with antiangiogenic and antitumor activity and the selectivity is higher 450-fold than other angiogenic receptors. |
靶点活性 | PDGFRα:10 nM, PDGFRβ:1 nM |
体外活性 | CP 673451 is a selective inhibitor of PDGFRα/β with IC50 of 10 nM/1 nM, exhibits >450-fold selectivity over other angiogenic receptors. In glioblastoma tumors, CP-673451 (33 mg/kg) provides >50% inhibition of PDGFR-β receptor for 4 hours corresponding to an EC50 of 120 ng/mL in plasma at Cmax. In a sponge angiogenesis model, CP-673451 inhibits 70% of PDGF-BB-stimulated angiogenesis at a dose of 3 mg/kg (q.d. ×5, p.o., corresponding to 5.5 ng/mL at Cmax).[1] CP-673451 decreases cell proliferation rate through mechanisms involving reduced phosphorylation of GSK-3α and GSK-3β. In both RD and RUCH2 cultures, CP-673451 impairs rhabdosphere-forming capacity and cell differentiation, causes increased senescence. [2] |
体内活性 | CP 673451 (once-daily p.o.) inhibits tumor growth (ED50 < 33 mg/kg) in a number of human tumor xenografts grown s.c. in athymic mice, including H460 human lung carcinoma, Colo205 and LS174T human colon carcinomas, and U87 mg human glioblastoma multiforme. [1] In RUCH2 xenograft-bearing mice, CP 673451 reduces tumor growth and stromal cell infiltration. [2] |
激酶实验 | Kinase inhibition assay: A glutathione S-transferase-tagged kinase domain construct of the intracellular portion of the PDGFR-β (amino acids 693-1401, accession no. J03278) is expressed in Sf-9 cells (baculovirus expression system). Enzyme kinetics are determined by incubating the enzyme with increasing concentrations of ATP in phosphorylation buffer [50 mmol/L HEPES (pH 7.3), 125 mmol/L NaCl, 24 mmol/L MgCl2 in Nunc Immuno MaxiSorp 96-well plates previously coated with 100 μL of 100 μg/mL poly-Glu-Tyr (4:1 ratio) diluted in PBS. After 10 minutes, the plates are washed (PBS, 0.1% Tween 20), incubated with anti-phosphotyrosine-horseradish peroxidase antibody, and diluted in PBS, 0.05% Tween 20, 3% BSA for 30 minutes at room temperature. The plates are washed as above and incubated with 3,3',5,5'-tetramethylbenzidine. The reaction is stopped by adding an equal volume of 0.09 NaH2SO4. The phosphotyrosine-dependent signal is then quantitated on a plate reader at 450 nm. For routine enzyme assays, the enzyme is incubated with 10 μM ( final) ATP in the presence of compound diluted in DMSO (1.6% v/v DMSO assay final) for 30 minutes at room temperature in plates, as above, previously coated with 100 μL of 6.25 μg/mL poly-Glu-Tyr. The remainder of the assay is carried out as above, and IC50 values are calculated as percent inhibition of control. |
细胞实验 | PAE cells stably expressing full-length PDGFR and VEGFR have been generated. For cell-based selectivity assays, PAE cells are transfected with fulllength human PDGFR-a, PDGFR-h, or VEGFR-2. Cells are seeded at 4×105 cells/mL in 50 μL growth medium (Ham's F-12 media supplemented with 10% fetal bovine serum, 50,000 units each penicillin and streptomycin, and 500 μg/mL gentamicin) per well in 96-well plates. After 6 to 8 hours, the growth medium is replaced with 50 μL serum-depleted medium (as above, but with 0.1% fetal bovine serum) and cells are incubated overnight. Immediately before compound addition, the medium was replaced with 95 μL serum-depleted medium. Compounds are diluted in 100% DMSO, added to the cells at a final DMSO concentration of 0.25% v/v, and incubated at 37°C for 10 minutes. Cells are stimulated with the appropriate ligand and incubated as above for an additional 8 minutes. The medium is removed and the cells washed once with PBS, then lysed with 50 μL HNTG buffer [20 mmol/L HEPES (pH 7.5), 150 mmol/L NaCl, 2% Triton X-100, 10% glycerol, 5 μmol/L EDTA, 2 mmol/L NaVO4, and 1 EDTA-free complete protease inhibitor tablet per 25 mL] for 5 minutes at room temperature. Lysates are then diluted with 50 μL HG buffer [20 mmol/L HEPES (pH 7.5), 10% glycerol]. The diluted cell lysates are mixed thoroughly, 50 μL of supernatant are transferred to the ELISA capture plate, and incubated at room temperature for 2 hours with agitation. ELISA capture plates are prepared by coating 96-well ReactiBind goat-antirabbit plates with 100 μL/well of 5 μg/mL rabbit anti-human PDGFR-h, anti-PDGFR-a, or anti-VEGFR-2 antibody for 60 to 90 minutes. At the end of the 2-hour incubation the plates are washed (PBS, 0.1% Tween 20) before incubation with anti-phosphotyrosine-horseradish peroxidase antibody (diluted in PBS, 0.05% Tween 20) for 30 minutes at room temperature. The plates are washed again, then incubated with tetramethylbenzidine and evaluated as described above.IC50 values are calculated as percent inhibition of control.(Only for Reference) |
分子量 | 417.5 |
分子式 | C24H27N5O2 |
CAS No. | 343787-29-1 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Ethanol: 41.8 mg/mL (100 mM)
DMSO: 41.8 mg/mL (100 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
Ethanol / DMSO | 1 mM | 2.3952 mL | 11.976 mL | 23.9521 mL | 59.8802 mL |
5 mM | 0.479 mL | 2.3952 mL | 4.7904 mL | 11.976 mL | |
10 mM | 0.2395 mL | 1.1976 mL | 2.3952 mL | 5.988 mL | |
20 mM | 0.1198 mL | 0.5988 mL | 1.1976 mL | 2.994 mL | |
50 mM | 0.0479 mL | 0.2395 mL | 0.479 mL | 1.1976 mL | |
100 mM | 0.024 mL | 0.1198 mL | 0.2395 mL | 0.5988 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。
CP-673451 343787-29-1 Angiogenesis Tyrosine Kinase/Adaptors c-Kit PDGFR VEGFR Inhibitor CP673451 inhibit CP 673451 Platelet-derived growth factor receptor inhibitor