PHARMACEUTICAL COMPOSITIONS COMPRISING RET INHIBITORS AND METHODS FOR THE TREATMENT OF CANCER

摘要

A class of compounds useful in pharmaceutical compositions and methods for treating or preventing cancer is described. The compounds' ability to inhibit RET kinase is quantified, i.e., their respective RET IC50 and EC50 values are described. One such compound, known as cyclobenzaprine and herein as SW-01, has been identified as RET-specific with an IC50 of 300 nM. SW-01 inhibits RET autophosphorylation and blocks the growth and transformation of thyroid cancer cell lines. It has been further tested in pancreatic cancer, breast cancer, and SCLC cell lines. The compounds show utility for inhibition of survival and proliferation of tumour cells.