VP79s

VP79s is a novel aryl-guanidinium based small molecule inhibitor developed by researchers at Trinity College Dublin for the treatment of multiple myeloma. It acts by targeting the JAK/STAT3 signaling pathway, specifically inhibiting the phosphorylation of Janus kinase 2 (JAK2) and downregulating the expression of interleukin-6 (IL-6) receptors CD126 and CD130. This dual action leads to a rapid, time-dependent decrease in the expression of the anti-apoptotic protein MCL-1, thereby inducing apoptosis in multiple myeloma cell lines. Preclinical studies have shown that VP79s is effective against both drug-sensitive and drug-resistant myeloma cells, can overcome adhesion-mediated drug resistance, and exhibits synergistic activity when combined with the proteasome inhibitor bortezomib.