Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases

SHP099, a selective inhibitor of signalling meditatorSHP2 with drug-like properties, has an allosteric mechanismof actionwhereby it stabilizes SHP2 in an auto-inhibited conformation, and suppresses RAS–ERK signalling and proliferation in receptor-tyrosine-kinase-driven cancer cell lines and mouse tumour xenograft models.