Design and synthesis of improved active-site SHP2 inhibitors with anti-breast cancer cell effects.

The Src homology containing phosphotyrosyl phosphatase 2 (SHP2) is a bona fide oncogene particularly in cancers driven by overexpression of receptor tyrosine kinases (RTKs). As such, there is a growing interest to target SHP2 in cancer. Based on these premises, several active site (type I) and allosteric site (type II) inhibitors have been developed, but no SHP2 targeting therapies have reached the clinic yet.