RapaLink-1

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上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

RapaLink-1  纯度: 97.93%

RapaLink-1 是第三代 mTOR 抑制剂，通过 linker 将雷帕霉素 (Rapamycin, HY-10219) 与二代 mTOR 抑制剂 MLN0128 (HY-13328) 结合。RapaLink-1 比雷帕霉素或 mTOR 抑制剂 (TORKi) 更有效，能有效地阻断癌源性的，激活的 mTOR 突变体。RapaLink-1 可以穿过血脑屏障。RapaLink-1 与 FKBP12 的结合导致持久抑制 mTORC1。RapaLink-1 通过促进自噬在抗磷脂综合征中发挥抗血栓作用。具有抗癌活性。

RapaLink-1

RapaLink-1 Chemical Structure

CAS No. : 1887095-82-0

规格 价格 是否有货 数量
1 mg ￥4900 In-stock
5 mg ￥7000 In-stock
10 mg ￥12500 In-stock
25 mg ￥20000 In-stock
50 mg   询价  
100 mg   询价  

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RapaLink-1 相关产品

•相关化合物库:

  • Bioactive Compound Library Plus
  • Macrocyclic Compound Library

生物活性

RapaLink-1, the third-generation bivalent mTOR inhibitor, combines Rapamycin (HY-10219) with MLN0128 (HY-13328, a second-generation mTOR kinase inhibitor) by an inert chemical linker. RapaLink-1 shows better efficacy than Rapamycin or mTOR kinase inhibitors (TORKi), potently blocking cancer-derived, activating mutants of mTOR. RapaLink-1 can cross the blood-brain barrier. RapaLink-1 binding to FKBP12 results in targeted and durable inhibition of mTORC1. RapaLink-1 plays an antithrombotic role in antiphospholipid syndrome by improving autophagy. Anticancer activity[1][2].

IC50 & Target[1]

mTOR

 

体外研究
(In Vitro)

RapaLink-1 (0-200 nM; 3 days) shows U87MG cells growth inhibition[1].
RapaLink-1 (0-12.5 nM; 48 hours) arrests U87MG cells at G0/G1[1].
RapaLink-1 selectively inhibits p-RPS6S235/236 and p-4EBP1T37/46 at doses as low as 1.56 nM[1].
Rapalink-1 (100 nM; 24 to 96 hours) suppressed renal cell carcinoma (RCC) cell proliferation by inducing apoptosis and cell cycle arrest[2].
RapaLink-1 exploits the unique juxtaposition of two drug-binding pockets to create a bivalent interaction. RapaLink-1 overcomes resistance to existing first- and second-generation inhibitors[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Proliferation Assay[1]

Cell Line: U87MG cells
Concentration: 0-200 nM
Incubation Time: 3 days
Result: Showed growth inhibition.

Cell Cycle Analysis[1]

Cell Line: U87MG cells
Concentration: 0-12.5 nM
Incubation Time: 48 hours
Result: Arrested cells at G0/G1.

Western Blot Analysis[1]

Cell Line: U87MG cells
Concentration: 0.39-12.5 nM
Incubation Time: 3 hours
Result: Selectively inhibited p-RPS6S235/236 and p-4EBP1T37/46 at doses as low as 1.56 nM. The mTORC2 targets p-AKTS473, p-SGK1S78, and p-NDRG1T346, and the p-AKTS473 target p-GSK3βS9 was inhibited only at high doses.

体内研究
(In Vivo)

RapaLink-1 (i.p.; every 5 days for 25 days, then once a week for 11 week) shows potent anti-tumor efficacy[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: BALB/ Cnu/nu mice bearing U87MG intracranial xenografts[1]
Dosage: 1.5 mg/kg
Administration: I.p.; every 5 days for 25 days, then once a week for 11 week
Result: Led to initial regression and subsequent stabilization of tumor size.

分子量

1784.14

Formula

C91H138N12O24
CAS 号

1887095-82-0
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
溶解性数据
In Vitro: 

DMSO : 178 mg/mL (99.77 mM; Need ultrasonic and warming)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 0.5605 mL 2.8025 mL 5.6049 mL
5 mM 0.1121 mL 0.5605 mL 1.1210 mL
10 mM 0.0560 mL 0.2802 mL 0.5605 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂： 10% DMSO    90% corn oil

    Solubility: ≥ 5 mg/mL (2.80 mM); Clear solution

    此方案可获得 ≥ 5 mg/mL (2.80 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例，取 100 μL 50.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Fan Q, et al. A Kinase Inhibitor Targeted to mTORC1 Drives Regression in Glioblastoma. Cancer Cell. 2017 Mar 13;31(3):424-435.

    [2]. Kuroshima K, et al. Potential new therapy of Rapalink-1, a new generation mammalian target of rapamycin inhibitor, against SU 11248-resistant renal cell carcinoma. Cancer Sci. 2020 May;111(5):1607-1618.

    [3]. Rodrik-Outmezguine VS, et al. Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature. 2016 Jun 9;534(7606):272-6.

    [4]. Mu F, et al. RapaLink-1 plays an antithrombotic role in antiphospholipid syndrome by improving autophagy both in vivo and vitro. Biochem Biophys Res Commun. 2020 Apr 30;525(2):384-391.

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