Rapalink-1

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Rapalink-1

本产品不向个人销售，仅用作科学研究，不用于任何人体实验及非科研性质的动物实验。

包装与价格：

包装	价格(元)
5mg	电议
25mg	电议

产品介绍

化学性质

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
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	为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。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。

资料参考

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.

试验操作

Cell experiment:[1]
Cell lines	Human glioma cell line U87MG
Reaction Conditions	0 ~ 200 nM Rapalink-1 for 3 days
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]
Animal models	BALB/C^nu/numice bearing U87MG intracranial xenografts
Dosage form	1.5 mg/kg Injected intraperitoneally (i.p.) every 5 or 7 days
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.
Note	The technical data provided above is for reference only.
	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.