Pim 1 kinase inhibitor ETP-45299 suppresses cellular proliferation and synergizes with PI3K inhibition

The serine/threonine Pim 1 kinase is an oncogene whose expression is deregulated in several human cancers Overexpression of Pim 1 facilitates cell cycle progression and suppresses apoptosis Hence pharmacologic inhibitors of Pim 1 are of therapeutic interest for cancer ETP-45299 is a potent and selective inhibitor of Pun 1 that inhibits the phosphorylation of Bad and 4EBP1 in cells and suppresses the proliferation of several non-solid and solid human tumor cell lines The combination of the PI3K inhibitor GDC-0941 with ETP-45299 was strongly synergistic in MV-4-11 AML cells indicating that the combination of selective Pim kinase inhibitors and PI3K inhibitor could have clinical benefit (C) 2010 Elsevier Ireland Ltd All rights reserved