Progress Toward Synthesis of Derivatives of Arp2/3 Complex Inhibitor CK-666

The Actin related Protein (Arp 2/3) is responsible for nucleating new actin filaments to create a branched network of actin. This activity is crucial for processes such as cell movement, endocytosis, and intracellular trafficking. The objective of the investigation is to establishing a reversible method of inhibiting the Arp 2/3 complex based on the known small-molecule Arp2/3 inhibitor CK-666. The use of CK-666 can prevent the motility of harmful pathogens across the cytoplasm of model organism cells. This project is also designed to provide a tool of use to researchers investigating the basic science of actin. The inhibitory strength of synthesized derivatives of CK-666 will be determined through a fluorescence assay to generate an IC50 value. The goal of the investigation involves developing an inhibitor with a lowered IC50 value. This research describes organic synthesis and biochemical testing of a derivative of CK-666 and synthetic efforts towards an azaindole derivative of CK-666.