PIM Kinase Inhibitors as Novel Promising Therapeutic Scaffolds in Cancer Therapy

Cancer is characterized by the uncontrolled and abnormal growth of cells, which can impact surrounding tissues. Kinases play a crucial role in cell proliferation and the development of cancer, with PIM kinase emerging as a potential therapeutic target. PIM kinases, which include isoforms PIM-1, PIM-2, and PIM-3, are associated with tumorigenesis through their role in phosphorylating proteins that regulate the cell cycle and cell proliferation. The expression of PIM genes is primarily controlled by the JAK/STAT signaling pathway, and PIM kinase is also linked to the PI3K/AKT/mTOR pathway across various cancer types. Overexpression of PIM kinase is known to contribute to cancer progression, prompting significant efforts in drug design aimed at its inhibition.

Several small chemical inhibitors, such as SGI-1776, AZD1208, and LGH447, have been developed to specifically target the ATP-binding domain of PIM proteins. These PIM kinase antagonists have demonstrated notable effects against different cancers. However, clinical trials for SGI-1776, the first PIM inhibitor, were prematurely discontinued, preventing it from providing definitive evidence of efficacy. Despite this setback, recent years have seen progress in identifying new PIM inhibitors. Compounds like cyanopyridines and pyrazolo[1,5-a]pyrimidines have shown promise as potent PIM kinase inhibitors for cancer therapy.

This article explores the role of the oncogenic transcription factor c-Myc and miRNA in relation to PIM kinase. We also provide insights into the oncogenic effects of PIM kinase and the structural characteristics of its inhibitors for potential cancer treatment.