产品说明书
CP-673451
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同义名 : | - |
| CAS号 : | 343787-29-1 | |
| 货号 : | A171069 | |
| 分子式 : | C24H27N5O2 | |
| 纯度 : | 99%+ | |
| 分子量 : | 417.503 | |
| MDL号 : | MFCD11100329 | |
| 存储条件： |
粉末 Keep in dark place,Sealed in dry,2-8°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 105 mg/mL(251.49 mM)，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 |
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| 动物实验配方： |
IP 2% DMSO+2% Tween80+40% PEG300+water 8 mg/mL clear PO 0.5% CMC-Na 18 mg/mL suspension |
| 生物活性 | |||
|---|---|---|---|
| 靶点 |
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| 描述 | The activating mutations of KIT or PDGFRα are important to the pathogenesis of tumors. CP-673451 is a potent and selective inhibitor of PDGFRα and PDGFRβ with IC50 values of 10nM and 1nM, respectively, with more than 250-fold selectivity for PDGFRβthan c-kit kinase, 450-5000 fold than other angiogenic tyrosine kinases, including VEGFR-1, VEGFR-2, TIE-2 and FGFR-2 (measured by kinase inhibition assay). Treatment with CP-673451 at concentration of 3-100nM caused dose-dependent inhibition of p-PDGFR induced by PDGF-BB with IC50 value of 6.4nM in PAE-PDGFR-βcells. Oral dose of 3, 10 and 30mg/kg CP-673451 daily for 5 days inhibited PDGF-BB-induced angiogenesis by 70%, 81% and 95% in the sponge model, with no obvious inhibition of bFGF-and VEGF165-induced antiangiogenesis at dose of 5mg/kg. Dose-dependent decrease of p-PDGFR by CP-673451 can be observed in C6 tumors treated with CP-673451 at 33mg/kg and 100mg/kg in ex vivo study. Oral treatment with CP-673451 q.d. or b.i.d. for 10-11 days caused tumor growth inhibition in U87MG xenografts by 80% at dose of 100mg/kg, LS174T xenografts by 64% at 50mg/kg, H460 xenografts by 80% at 33mg/kg and Colo205 xenografts by 75% at 33mg/kg. Reduction of microvascular density up to 47% can be observed in tumors of Colo205-bearing mice dosed with 5mg/kg CP-673451 twice daily for 5 days. Combination of 33mg/kg CP-673451 once daily for 10 days with 10mg/kg Paclitaxel dosed once daily on days 1 to 5 caused tumor growth inhibition by 88%, compared with the agent alone by 49% or 54%, in mice bearing LS174T human colon adenocarcinoma xenografts[1]. | ||
| 作用机制 | CP-673451 is an ATP-competitive inhibitor of PDGFR.[1] | ||
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
2.40mL 0.48mL 0.24mL |
11.98mL 2.40mL 1.20mL |
23.95mL 4.79mL 2.40mL |
