RPI-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

RPI-1 是一种竞争性、有效的 ATP 依赖性 Ret 激酶抑制剂。

RPI-1 is an ATP-dependent RET kinase inhibitor. Oral treatment with RPI-1 caused growth arrest or regression in 81% treated tumors. Following treatment suspension, tumor inhibition was maintained (51%, P<0.05, 100 days) and cures were achieved in 2/11 mice. In vivo effects of RPI-1 were reflected in activation of BAD, cleavage of caspases, apoptotic DNA fragmentation and inhibition of VEGF production observed in in vitro RPI-1-treated TT cells..

TPC-1 cells are sensitive to the growth inhibitory effect of RPI-1 with an IC50 of 5.1 μM, following 72 hours of treatment. RPI-1 (7.5-60 μM) inhibits Ret/Ptc1 autophosphorylation in TPC-1 cells. RPI-1 inhibitory effects in the TPC-1 cell culture conditions lead to inhibition of pathways involving JNK2 and AKT.The RPI-1 IC50 value for cell proliferation is 3.6 μM in NIH3T3 cells expressing the Ret mutant compared with 16 μM in non-transfected NIH3T3 cells, and that for colony formation in soft agar was 2.4 μM and 26 μM in RET mutant-transfected and H-RAS-transfected NIH3T3 cells, respectively. In NIH3T3 cells expressing the Ret mutant, Ret protein and tyrosine phosphorylation were undetectable after 24 hours of RPI-1 treatment. In TT cells, RPI-1 inhibits proliferation, Ret tyrosine phosphorylation, Ret protein expression, and the activation of PLCgamma, ERKs and AKT.

RPI-1 (50, 100 mg/kg; p.o.; twice a day for 10 days) inhibits the tumor growth of TT xenografts by 81%. Animal Model:8- to 11-week-old female athymic nude CD-1 mice (bearing TT cells)Dosage:50, 100 mg/kg Administration: P.o.; twice a day for 10 days Result:A dose-dependent effect on tumor growth was observed, with a dose of 2*50 mg/kg/day resulting in less tumor weight inhibition than the 2*100mg/kg/day dose after 10 days of treatment.

RPI-1 | RPI1 | RPI 1

Endocrinology/Hormones

AChR

Met| RET| CTND1| DCDB2| PLCγ

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269730-03-2

297.31

C17H15NO4

>98% (HPLC)

In Vitro:?DMSO : 125 mg/mL (420.44 mM)

COc1c(cc2c(c1)/C(=C/c1ccc(cc1)O)/C(=O)N2)OC

1,3-dihydro-3-[(4-hydroxyphenyl)methylene]-5,6-dimethoxy-2H-indol-2-one

(-20℃)

With Ice Pack

≥ 2 years