Synthesis of CK-869 Derivatives as Potential Inhibitors of the Arp2/3 Complex

The Actin related protein 2 and 3 complex is (Arp2/3) is a key protein allowing for polymerization necessary to the actin cytoskeleton that aids in cytokinesis, endocytosis, and cellular motility. The Arp 2/3 complex is a seven-subunit protein that allows for the polymerization of actin within a cell by acting as a nucleation site for daughter actin filaments to branch from pre-existing filament strands. The inhibition of Arp 2/3 complex can prevent the motility of harmful pathogens by inhibiting actin comet tail formation. This research may provide further knowledge on the basic science of actin by allowing one specific part of the actin polymerization process to be inhibited. This work is intended to produce Arp 2/3 inhibitors with significantly increased potency compared to commercially available inhibitors. The research described resulted in synthesis of derivatives of CK-869, an Arp 2/3 inhibitor, and their potency was determined through a standard bulk actin polymerization in vitro assay.