RPI-1

Names

[ Name ]:
RPI-1

[Synonym ]:
(3Z)-3-(4-Hydroxybenzylidene)-5,6-dimethoxy-1,3-dihydro-2H-indol-2-one
1,3-dihydro-5,6-dimethoxy-3-((4-hydroxyphenyl)methylene)-2H-indol-2-one
2H-Indol-2-one, 1,3-dihydro-3-[(4-hydroxyphenyl)methylene]-5,6-dimethoxy-, (3Z)-
RPI-1

Biological Activity

[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].

[Related Catalog]:

Research Areas >> Cancer

[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].

[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.

[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.

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
533.6±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₇H₁₅NO₄

[ Molecular Weight ]:
297.305

[ Flash Point ]:
276.5±30.1 °C

[ Exact Mass ]:
297.100098

[ PSA ]:
67.79000

[ LogP ]:
3.08

[ Vapour Pressure ]:
0.0±1.5 mmHg at 25°C

[ Index of Refraction ]:
1.660

Safety Information

[ Symbol ]:

GHS09

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H400

[ Precautionary Statements ]:
P273

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ RIDADR ]:
UN 3077 9 / PGIII

Articles

Proteomic Identification of DNA-PK Involvement within the RET Signaling Pathway.

PLoS ONE 10 , e0127943, (2015)

Constitutive activation of the Rearranged during Transfection (RET) proto-oncogene leads to the development of MEN2A medullary thyroid cancer (MTC). The relatively clear genotype/phenotype relationshi...

Glial cell line-derived neurotrophic factor induces cell proliferation in the mouse urogenital sinus.

Mol. Endocrinol. 29(2) , 289-306, (2015)

Glial cell line-derived neurotrophic factor (GDNF) is a TGFβ family member, and GDNF signals through a glycosyl-phosphatidylinositol-linked cell surface receptor (GFRα1) and RET receptor tyrosine kina...