Ontology highlight
ABSTRACT:
SUBMITTER: Andrews FH
PROVIDER: S-EPMC5320964 | biostudies-literature | 2017 Feb
REPOSITORIES: biostudies-literature
Andrews Forest H FH Singh Alok R AR Joshi Shweta S Smith Cassandra A CA Morales Guillermo A GA Garlich Joseph R JR Durden Donald L DL Kutateladze Tatiana G TG
Proceedings of the National Academy of Sciences of the United States of America 20170130 7
<i>MYC</i> is a major cancer driver but is documented to be a difficult therapeutic target itself. Here, we report on the biological activity, the structural basis, and therapeutic effects of the family of multitargeted compounds that simultaneously disrupt functions of two critical MYC-mediating factors through inhibiting the acetyllysine binding of BRD4 and the kinase activity of PI3K. We show that the dual-action inhibitor impairs PI3K/BRD4 signaling in vitro and in vivo and affords maximal M ...[more]