Rapalink-1
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
RapaLink-1是第三代mTOR抑制剂,它将第一代和第二代mTOR激酶抑制剂的结合口袋进行独特结合,创造了一个二价的相互作用,使得其能抑制对之前的TORKi (mTOR激酶抑制剂) 具有抗性的突变.
PIK3CA–AKT–mTOR信号通路是人类癌症中最常见的被激活的通路之一,这使得靶向这条信号通路多个节点的小分子抑制剂的发展.已经有两代mTOR抑制剂被开发出来.
Rapalink-1相比于第一代和第二代mROR抑制剂更加强效.Rapalink-1能够更加有效的减少p-4EBP1的量和细胞增殖.研究者在LN229和U87MG细胞中对比了rapamycin, RapaLink-1, 和MLN0128的药效.相比于rapamycin或MLN0128,RapaLink-1表现出了更强的生长抑制和使细胞停滞在G0/G1期的能力.在体内RapaLink-1表现出了强力的抗肿瘤效力,在异种移植瘤模型中,它导致肿瘤消退和随后的肿瘤体积的稳定,而使用媒介,rapamycin或MLN0128的组别肿瘤稳定的生长.
RapaLink-1能够持久的阻滞mTORC1.RapaLink-1与FKBP12,丰富的mTOR相互作用蛋白相关,这使得RapaLink-1能够聚集起来.相比于rapamycin或其它的TORKi,RapaLink-1表现出更好的疗效,能够强效的阻碍癌症来源的mTOR激活型突变.
References:
[1]. Fan Q1, Aksoy O1, Wong RA1, et al, A Kinase Inhibitor Targeted to mTORC1 Drives Regression in Glioblastoma. Cancer Cell. 2017 Mar 13;31(3):424-435. doi: 10.1016/j.ccell.2017.01.014.
[2] Rodrik-Outmezguine VS1, Okaniwa M2, Yao Z1, et al, Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor. Nature. 2016 Jun 9;534(7606):272-6. doi: 10.1038/nature17963. Epub 2016 May 18.
- 1. Erin M O'Leary, Yufeng Tian, et al. "TGF-β Promotes Metabolic Reprogramming in Lung Fibroblasts via mTORC1-dependent ATF4 Activation." Am J Respir Cell Mol Biol. 2020 Nov;63(5):601-612. PMID:32668192
- 2. Kuroshima K, Yoshino H, et al. "Potential new therapy of Rapalink-1, a new generation mammalian target of rapamycin inhibitor, against sunitinib-resistant renal cell carcinoma." Cancer Sci. 2020;111(5):1607-1618. PMID:32232883
| Storage | Store at -20°C |
| M.Wt | 1784.14 |
| Formula | C91H138N12O24 |
| Solubility | ≥178.4 mg/mL in DMSO; insoluble in H2O; ≥24.85 mg/mL in EtOH |
| SDF | Download SDF |
| Canonical SMILES | O=C(NCCCCN1N=C(C2=CC=C(OC(N)=N3)C3=C2)C4=C(N)N=CN=C41)CCOCCOCCOCCOCCOCCOCCOCCOCCN5C=C(COCCO[C@@H]6CC[C@@H](C[C@H]([C@@H](OC([C@H](CCCC7)N7C(C([C@@]8(O)[C@H](C)CC[C@H](O8)C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C([C@H](OC)[C@H](O)/C(C)=C/[C@H]9C)=O)=O |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| Cell experiment:[1] | |
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Cell lines |
Human glioma cell line U87MG |
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Reaction Conditions |
0 ~ 200 nM Rapalink-1 for 3 days |
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Applications |
In U87MG cells, both growth inhibition (0 ~ 200 nM Rapalink-1; 3 days) and arrest in G0/G1 (0 ~ 12.5 nM Rapalink-1; 48 hours) were more obvious in response to Rapalink-1, compared with Rapamycin or MLN0128. |
| Animal experiment:[1] | |
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Animal models |
BALB/Cnu/nu mice bearing U87MG intracranial xenografts |
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Dosage form |
1.5 mg/kg Injected intraperitoneally (i.p.) every 5 or 7 days |
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Applications |
Rapalink-1 led to initial regression and subsequent stabilization of tumor size, while tumors treated with vehicle, Rapamycin, or MLN0128 grew steadily. Furthermore, Rapalink-1 was well tolerated and associated with significantly improved survival. |
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Note |
The technical data provided above is for reference only. |
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References: 1. Fan Q, Aksoy O, Wong RA, et al. A kinase inhibitor targeted to mTORC1 drives regression in glioblastoma. Cancer Cell, 2017, 31(3): 424-435. |
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质量控制和MSDS
- 批次:
化学结构
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