PIM2

PIM2 is a serine/threonine kinase that supports cell survival and proliferation, and early work defined Pim-2 as a transcriptionally regulated apoptotic inhibitor^[1]. Mechanistically, PIM2 phosphorylates BAD at Ser112 and reverses BAD-induced cell death, linking PIM2 kinase activity to anti-apoptotic signaling^[2]. In multiple myeloma, Pim2 expression is highly elevated and is required for myeloma cell proliferation through TSC2 phosphorylation and mTORC1 modulation^[3]. PIM2 kinase also supports plasmablast generation and plasma cell survival, connecting B-cell differentiation models with myeloma research applications^[4]. Compared with related isoforms, PIM2 shares 55% sequence identity with PIM1, but structural differences between PIM1 and PIM2 may guide isoform-selective inhibitor design^[5]. In BAD phosphorylation assays, Pim-2 predominantly phosphorylated Ser112, whereas Pim-3 was least specific for Ser112 and more effective at Ser136 and Ser155^[6]. For experimental applications, the pan-PIM inhibitor PIM447 showed preclinical antimyeloma and bone-protective effects, while first-in-human studies evaluated oral PIM447 in relapsed or refractory multiple myeloma^[7][8].