RapaLink-1

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

RapaLink-1 是第三代 mTOR 抑制剂，克服了现有第一代和第二代抑制剂的耐药性。

RapaLink-1 is a third-generation mTOR inhibitor that overcomes resistance to existing first- and second-generation inhibitors; blocks mTOR signaling of the F2108L mTOR and M2327I mTOR drug resistant mutants; RapaLink-1 is more potent mTOR inhibitor than rapamycin.

RapaLink-1 (0-200 nM; 3 days) shows U87MG cells growth inhibition.RapaLink-1 (0-12.5 nM; 48 hours) arrests U87MG cells at G0/G1.RapaLink-1 selectively inhibits p-RPS6S235/236 and p-4EBP1T37/46 at doses as low as 1.56 nM. Rapalink-1 (100 nM; 24 to 96 hours) suppressed renal cell carcinoma (RCC) cell proliferation by inducing apoptosis and cell cycle arrest.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. :Cell Proliferation Assay Cell Line:U87MG cells Concentration:0-200 nM Incubation Time:3 days Result:Showed growth inhibition.Cell Cycle Analysis Cell Line:U87MG cells Concentration:0-12.5 nM Incubation Time:48 hours Result:Arrested cells at G0/G1.Western Blot Analysis 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.

RapaLink-1 (i.p.; every 5 days for 25 days, then once a week for 11 week) shows potent anti-tumor efficacy. Animal Model:BALB/ Cnu/nu mice bearing U87MG intracranial xenografts 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.

RapaLink 1 | RapaLink1

PI3K/Akt/mTOR signaling

mTOR

mTOR

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1887095-82-0

1784.165

C91H138N12O24

>98% (HPLC)

In Vitro:?DMSO : 178 mg/mL (99.77 mM)

CC1CCC2CC(C(=CC=CC=CC(CC(CC(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O)C(C)CC4CCC(C(C4)OC)OCCOCC5=CN(N=N5)CCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCCCN6C7=NC=NC(=C7C(=N6)C8=CC9=C(C=C8)OC(=N9)N)N)C)C)O)OC)C)C)C)OC

40-O-(2-((1-(32-(4-amino-3-(2-aminobenzo[d]oxazol-5-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-27-oxo-3,6,9,12,15,18,21,24-octaoxa-28-azadotriacontyl)-1H-1,2,3-triazol-4-yl)methoxy)ethyl)-rapamycin

(-20℃)

With Ice Pack

≥ 2 years