产品说明书
RapaLink-1
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同义名 : | - |
| CAS号 : | 1887095-82-0 | |
| 货号 : | A656890 | |
| 分子式 : | C91H138N12O24 | |
| 纯度 : | 95% | |
| 分子量 : | 1784.136 | |
| MDL号 : | MFCD32633594 | |
| 存储条件： |
粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C 液体 -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 175 mg/mL(98.09 mM)，配合低频超声，并水浴加热至45℃助溶，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： |
| 生物活性 | |||
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| 描述 | RapaLink-1 is the third-generation mTOR inhibitor which can overcome mTOR resistance mutations. It exploits the unique juxtaposition of two drug-binding pockets to create a bivalent interaction that allows inhibition of these resistant mutants, and reverses resistance due to mTOR FRB (resistant to Rapamycin) and kinase domain (resistant to AZD8055) mutations. RapaLink-1 is a potent mTOR inhibitor evidenced by suppression of downstream signaling, including p-AKT, p-p70S6K, p-S6 and p-4EBP1, in MCF-7 cells treated with RapaLink-1 at concentration>3nM post 4h. RapaLink-1 at low doses (3–10 nM) was the only drug regimen capable of inhibiting mTOR signalling in both F2108L mTOR- and M2327I mTOR-expressing cells. Administration of 1.5mg/kg RapaLink-1, i.p., weekly, significantly inhibited tumor growth in mice bearing RR1 or TKi-R xenograft tumors[3]. RapaLink-1 crosses the blood-brain barrier. RapaLink-1 drove regression of intracranial brain cancers in vivo, improving survival compared with earlier-generation inhibitors, first-generation allosteric mTOR inhibitor rapamycin and second-generation TORKi[4]. | ||
| 作用机制 | RapaLink-1 is consist of MLN0128 targeting the ATP-site and Rapamycin targeting FRB/FKBP12-site, which facilitates it to exploit the unique juxtaposition of two drug-binding pockets to create a bivalent interaction that allows inhibition of these resistant mutants.[3] | ||
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
0.56mL 0.11mL 0.06mL |
2.80mL 0.56mL 0.28mL |
5.60mL 1.12mL 0.56mL |
| 参考文献 |
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