How does SGI-1776 affect global RNA synthesis in MCL cell lines?

SGI-1776 is a Pim kinase inhibitor that targets transcription and translation processes in MCL cells. Pim kinases are involved in stabilizing c-Myc, which drives transcription, and in regulating translation through 4E-BP1 phosphorylation.

SGI-1776 significantly reduces global RNA synthesis in MCL cell lines such as JeKo-1, Mino, Granta 519, and SP-53. In JeKo-1 cells, RNA synthesis decreases to 75%, 57%, and 28% of control at 3, 5, and 10 µM of SGI-1776, respectively. In Mino cells, RNA synthesis slightly increases at lower concentrations but decreases by 40% at 10 µM. This reduction in RNA synthesis is associated with decreased levels of short-lived mRNA and proteins like Mcl-1 and cyclin D1, contributing to cell death.