Proviral integration site for Moloney murine leukemia virus 1 kinase (Pim-1)

Proviral integration site for Moloney murine leukemia virus 1 kinase (Pim-1) is a serine/threonine kinase first identified due to its upregulation following proviral insertion during retroviral-induced tumorigenesis[1]. Pim-1 regulates numerous cellular processes including cell survival, proliferation, differentiation, apoptosis, and the development of cancer through phosphorylation of a range of substrates (such as Myc, p21^Cip1/WAF1^, p27^KIP1^, and BAD)[1][2][4]. It is induced by multiple cytokines, largely through JAK/STAT pathways, and is often overexpressed in various malignancies, including hematological and solid tumors[1][2]. Pim-1 is a validated therapeutic target with several small molecule inhibitors (such as AZD1208) in clinical development, demonstrating antiproliferative and pro-apoptotic effects in cancer models[2][4]. Besides its oncogenic role, Pim-1 is involved in T helper cell differentiation and immune response modulation[3]. Safety concerns in targeting Pim-1 center around unintended effects on normal tissue proliferation and immune regulation[2].

Other names

Pim-1Proviral integration site for Moloney murine leukemia virus 1PIM1 kinaseProto-oncogene Pim-1

ATP-competitive inhibition of kinase activity Suppression of Pim-1 levels leading to cell cycle arrest and apoptosis Decreased phosphorylation of substrates such as BAD, 4E-BP1, p70S6K, and S6 proteins Downregulation of proto-oncogenic signaling