Ontology highlight
ABSTRACT:
SUBMITTER: Chaikuad A
PROVIDER: S-EPMC4687050 | biostudies-literature | 2014 Oct
REPOSITORIES: biostudies-literature
Chaikuad Apirat A Tacconi Eliana M C EM Zimmer Jutta J Liang Yanke Y Gray Nathanael S NS Tarsounas Madalena M Knapp Stefan S
Nature chemical biology 20140907 10
Activation of the ERK pathway is a hallmark of cancer, and targeting of upstream signaling partners led to the development of approved drugs. Recently, SCH772984 has been shown to be a selective and potent ERK1/2 inhibitor. Here we report the structural mechanism for its remarkable selectivity. In ERK1/2, SCH772984 induces a so-far-unknown binding pocket that accommodates the piperazine-phenyl-pyrimidine decoration. This new binding pocket was created by an inactive conformation of the phosphate ...[more]