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. ■ SIGNIFICANCEA concise summary of research in the field of PIM inhibition for cancer, with a focus on medicinal chemistry, is presented. An analysis of current compounds entering clinical trials highlights existing issues and provides viewpoints on potential solutions. Future prospects and recommendations for development are discussed, emphasizing the need for unique perspectives and analyses in medicinal chemistry to stimulate critical thinking, expand understanding, and advance research in this field.