AA3-FIBA-BA8

AA3-FIBA-BA8 is an experimental small-molecule inhibitor of MEK (mitogen-activated protein kinase kinase) identified through a miniaturized nanodroplet array platform. This platform integrates high-throughput combinatorial synthesis, MALDI-MSI characterization, and cell-based screening within 200 nL droplets. AA3-FIBA-BA8 targets the MAPK/ERK signaling pathway, which is frequently dysregulated in colorectal and pancreatic cancers. Mechanistically, it acts as an allosteric, non-competitive inhibitor of MEK, binding to a site distinct from the ATP-binding pocket. In preclinical screenings, AA3-FIBA-BA8 demonstrated significant cytotoxicity against cancer cell lines, reportedly exceeding the potency of the clinically approved MEK inhibitor mirdametinib. The compound was developed as part of a library of 325 MEK inhibitors to demonstrate the efficiency of integrated miniaturized drug discovery platforms.