Comprehensive Insights that Targeting PIM for Cancer Therapy: Prospects and Obstacles.

ABSTRACT

Proviral integration sitea for Moloney-murine leukemia virus (PIM) kinases are a family of highly conserved serine/tyrosine kinases consisting of three members, PIM-1, PIM-2, and PIM-3. These kinases regulate a wide range of substrates through phosphorylation and affect key cellular processes such as transcription, translation, proliferation, apoptosis, and energy metabolism. Several PIM inhibitors are currently undergoing clinical trials, such as a phase I clinical trial of Uzanserti (5) for the treatment of relapsed diffuse large B-cell lymphoma that has been completed. The current focus encompasses the structural and biological characterization of PIM, ongoing research progress on small-molecule inhibitors undergoing clinical trials, and evaluation analysis of persisting challenges in this field. Additionally, the design and discovery of small-molecule inhibitors targeting PIM in recent years have been explored, with a particular emphasis on medicinal chemistry, aiming to provide valuable insights for the future development of PIM inhibitors.