RPI-1 is an ATP-dependent Ret tyrosine kinase inhibitor [1]. The ret proto-oncogene encodes a receptor protein tyrosine kinase involved in the etiology of human tumors. RET loss of function mutations are associated with the development of Hirschsprung's disease, and gain of function mutations are associated with the development of various types of human cancer, including medullary thyroid carcinoma, multiple endocrine neoplasias, pheochromocytoma and parathyroid hyperplasia. In NIH3T3 fibroblasts expressing the Ret/ptc1 target tyrosine kinase (NIH3T3ptc1), RPI-1 preferentially inhibited the anchorage-independent growth with IC50 value of 0.97 µM [1]. In the N592 SCLC and H460 NSCLC cell lines, RPI-1 dose-dependently inhibited Met phosphorylation.
