Actin is a family of globular multi-functional proteins that form microfilaments. Microfilaments, also called actin filaments, are filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. Actin participates in many important cellular processes, including muscle contraction, cell motility, cell division and cytokinesis, vesicle and organelle movement, cell signaling, and the establishment and maintenance of cell junctions and cell shape.
Actin-related protein 2/3 (ARP2/3) complex is an actin nucleator responsible for actin cytoskeleton branching which is essential for efficient cell migration. Cellular movement is essential to several normal biological processes, such as the activities of the immune system and tissue repair and regeneration, while aberrantly activated cell migration is involved in many diseases. For example, in cancer, acquired cell migration ultimately leads to lethal metastatic disease. Thus, Inhibiting the ARP2/3 complex subunits typically results in reduced cell migration capacity and provides insight into the mechanisms regulating metastases in cancer.
CK-666 stabilizes the inactive state of the ARP2/3 complex, blocking movement of the Arp2 and Arp3 subunits into the activated filament-like (short pitch) conformation. In other words, CK-666 is a ARP 2/3 complex inhibitor. It acts as a cell-permeable selective inhibitor of actin assembly mediated by actin-related protein Arp2/3 complex.
- Small molecules CK-666 and CK-869 inhibit actin-related protein 2/3 complex by blocking an activating conformational change – Hetrick B1, Han MS, Helgeson LA, Nolen BJ
- Characterization of two classes of small molecule inhibitors of Arp2/3 complex – Nolen BJ1, Tomasevic N, Russell A, Pierce DW, Jia Z, McCormick CD, Hartman J, Sakowicz R, Pollard TD.