ISIS 4559

ISIS 4559 is a phosphorothioate antisense oligonucleotide (ASO) designed to selectively inhibit the expression of Protein Kinase C alpha (PKC-α). PKC-α is a member of the serine/threonine protein kinase family that plays a critical role in signal transduction pathways governing cell proliferation, differentiation, and apoptosis. In many cancers, particularly glioblastoma multiforme (GBM), PKC-α is overexpressed and acts as an anti-apoptotic survival factor. ISIS 4559 functions by binding to the PKC-α mRNA through Watson-Crick base pairing, which induces RNase H-mediated cleavage of the mRNA transcript. This results in the downregulation of PKC-α protein levels, which has been shown to trigger p53-dependent apoptosis and increase the expression of insulin-like growth factor-binding protein-3 (IGFBP3). Developed by Ionis Pharmaceuticals (formerly ISIS Pharmaceuticals), ISIS 4559 has been primarily investigated in preclinical and early research models of malignant gliomas.