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。
| 生物活性 | RapaLink-1, the third-generation bivalentmTORinhibitor, combines Rapamycin (HY-10219) with MLN0128 (HY-13328, a second-generationmTORkinase inhibitor) by an inert chemical linker. RapaLink-1 shows better efficacy than Rapamycin ormTORkinase inhibitors (TORKi), potently blocking cancer-derived, activating mutants ofmTOR. RapaLink-1 can cross the blood-brain barrier. RapaLink-1 binding to FKBP12 results in targeted and durable inhibition ofmTORC1. RapaLink-1 plays an antithrombotic role in antiphospholipid syndrome by improvingautophagy. Anticancer activity[1][2]. |
| IC50& Target[1] | |
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-RPS6S235/236and p-4EBP1T37/46at 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].
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-RPS6S235/236and p-4EBP1T37/46at doses as low as 1.56 nM. The mTORC2 targets p-AKTS473, p-SGK1S78, and p-NDRG1T346, and the p-AKTS473target p-GSK3βS9was 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].
| 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 | |
| 性状 | |
| Formula | |
| CAS 号 | |
| 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 | 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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 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本网站选购。 |
m.cnreagent.com