Скачать или смотреть Small Molecule Inhibitors of Oncogenic SHP2 Variants Characterized by Cellular Target Engagement

The discovery of small molecules inhibitors that target oncogenic forms of SHP2 phosphatase holds great therapeutic promise for cancer patients. SHP2 phosphatase, also known as Src-homology 2 (SH2) domain-containing tyrosine phosphatase 2 encoded by PTPN11, is a key mediator of the Ras/Raf/ERK pathway. Aberrant SHP2 function contributes to the development, progression and metastasis of many cancers. Currently, a single class of allosteric SHP2 inhibitors has entered clinical trials, but they are not effective against oncogenic SHP2 variants found in leukaemias. Therefore, the discovery of small molecules that can target these oncogenic forms of SHP2 is needed.

A common problem in most drug discovery campaigns is that the primary in vitro assays that drive discovery do not assess the cellular target engagement of candidate compounds. We developed a cellular target engagement platform based on Eurofins DiscoverX InCELL Pulse™ for both wild-type and oncogenic SHP2 mutants.