Small-molecule inhibitors of actin dynamics and cell motility

Cell motility is a central feature of a range of normal and pathological processes, including embryonic development, tissue repair, immune cell function, angiogenesis, and cancer metastasis. The dynamics of the actin cytoskeleton power cell migration. A large number of proteins are known or suspected to play roles in regulating actin dynamics. While there are now many available small molecules that target the actin cytoskeleton directly, there is a paucity of specific inhibitors of actin-binding proteins and other immediate regulators of actin dynamics and cell movement. This makes the field of exceptional interest as a meeting place between the goals of chemical biology and the needs of cell biology. Furthermore, while regulators of the cell cycle have been recognized for some time as targets for anti-cancer drug development, controlling actin dynamics and cell motility as a therapeutic approach has received scant attention in comparison until recently. This review deals with small-molecule inhibitors of actin dynamics as they relate to cell shape change and motility, from compounds targeting actin directly to those targeting proteins involved in the fundamental control of the actin cytoskeleton.