Home
Resources
Publications
Diarylureas Are Small-Molecule Inhibitors of Insulin-Like Growth Factor I Receptor Signaling and Breast Cancer Cell Growth

Diarylureas Are Small-Molecule Inhibitors of Insulin-Like Growth Factor I Receptor Signaling and Breast Cancer Cell Growth

Karissa L Gable, Betty A Maddux, Cristina Penaranda, Marianna Zavodovskaya, Michael J Campbell, Margaret Lobo, Louise Robinson, Steven Schow, John A Kerner, Ira D Goldfine, Jack F Youngren

Mol Cancer Ther. 2006 Apr;5(4):1079-86.

PMID: 16648580

Abstract:

In breast and certain other cancers, receptor tyrosine kinases, including the insulin-like growth factor I receptor (IGF-IR), play an important role in promoting the oncogenic process. The IGF-IR is therefore an important target for developing new anti-breast cancer therapies. An initial screening of a chemical library against the IGF-IR in breast cancer cells identified a diaryl urea compound as a potent inhibitor of IGF-IR signaling. This class of compounds has not been studied as inhibitors of the IGF-IR. We studied the effectiveness of one diaryl urea compound, PQ401, at antagonizing IGF-IR signaling and inhibiting breast cancer cell growth in culture and in vivo. PQ401 inhibited autophosphorylation of the IGF-IR in cultured human MCF-7 cells with an IC50 of 12 micromol/L and autophosphorylation of the isolated kinase domain of the IGF-IR with an IC50 <1 micromol/L. In addition, PQ401 inhibited the growth of cultured breast cancer cells in serum at 10 micromol/L. PQ401 was even more effective at inhibiting IGF-I-stimulated growth of MCF-7 cells (IC50, 6 micromol/L). Treatment of MCF-7 cells with PQ401 was associated with a decrease in IGF-I-mediated signaling through the Akt antiapoptotic pathway. Twenty-four hours of treatment with 15 micromol/L PQ401 induced caspase-mediated apoptosis. In vivo, treatment with PQ401 (i.p. injection thrice a week) reduced the growth rate of MCNeuA cells implanted into mice. These studies indicate that diaryl urea compounds are potential new agents to test in the treatment of breast and other IGF-I-sensitive cancers.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP196868630-B	PQ401		196868-63-0	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: