RPI-1

Cas No.:	269730-03-2
Chemical Name:	RET Receptor Tyrosine Kinase Inhibitor; 1,3-dihydro-5,6-dimethoxy-3-[(4-hydroxyphenyl)methylene]-H-indol-2-one; (3E)-3-[(4-hydroxyphenyl)methylidene]-5,6-dimethoxy-1H-indol-2-one
Synonyms:	RPI1,RPI 1
SMILES:	C1=C(O)C=CC(/C=C2/C3=CC(OC)=C(OC)C=C3NC/2=O)=C1
Formula:	C17H15NO4
M.Wt:	297.31
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	RPI-1 is a specific, orally available 2-indolinone Ret tyrosine kinase inhibitor. RPI-1 inhibits proliferation, Ret tyrosine phosphorylation, Ret protein expression, and the activation of PLCgamma, ERKs and AKT in human medullary thyroid carcinoma TT cells. Antitumor activity[1].
In Vivo:	RPI-1 (50, 100 mg/kg; p.o.; twice a day for 10 days) inhibits the tumor growth of TT xenografts by 81%[2]. Animal Model: 8- to 11-week-old female athymic nude CD-1 mice (bearing TT cells)[2] 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.
In Vitro:	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[1]. 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[2].
References:	[1]. Lanzi C, et al. Inactivation of Ret/Ptc1 oncoprotein and inhibition of papillary thyroid carcinoma cell proliferation by indolinone RPI-1. Cell Mol Life Sci. 2003;60(7):1449-1459. [2]. Cuccuru G, et al. Cellular effects and antitumor activity of RET inhibitor RPI-1 on MEN2A-associated medullary thyroid carcinoma. J Natl Cancer Inst. 2004;96(13):1006-1014.