Proviral integration site for Moloney murine leukemia virus kinases (PIM kinases) (PIM kinases)

The Proviral integration site for Moloney murine leukemia virus (PIM) kinases are a family of three highly conserved serine/threonine kinases (PIM1, PIM2, and PIM3) that function as downstream effectors of many cytokine and growth factor receptors [1][2]. These kinases are unique because they are constitutively active and primarily regulated at the levels of transcription and protein stability, often via the JAK/STAT signaling pathway [3][4]. PIM kinases promote cell survival and proliferation by phosphorylating various substrates, including the pro-apoptotic protein BAD and the cell cycle regulator Cdc25A, thereby bypassing normal growth control mechanisms [4][5]. They are frequently overexpressed in a wide range of malignancies, including multiple myeloma, acute myeloid leukemia, and various solid tumors, where they contribute to chemoresistance and disease progression [1][6]. Pan-PIM inhibitors are designed to target all three isoforms simultaneously to overcome functional redundancy among the family members [6][7]. While several pan-PIM inhibitors have entered clinical trials, challenges such as gastrointestinal toxicity and QTc prolongation have been noted, leading to ongoing efforts to optimize their safety profiles and identify synergistic drug combinations [7][8].

Other names

PIM family kinasesPIM-1/2/3Serine/threonine-protein kinase pim-1Serine/threonine-protein kinase pim-2Serine/threonine-protein kinase pim-3

ATP-competitive inhibition of PIM1, PIM2, and PIM3 isoforms [4][7]