Structural Characterization and Computer??Aided Optimization of a Small??Molecule Inhibitor of the Arp2/3 Complex, a Key Regulator of the Actin Cytoskeleton

AW Baggett, Z Cournia, MS Han, G Patargias…

Index: Baggett, Andrew W.; Cournia, Zoe; Han, Min Suk; Patargias, George; Glass, Adam C.; Liu, Shih-Yuan; Nolen, Brad J. ChemMedChem, 2012 , vol. 7, # 7 p. 1286 - 1294

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Citation Number: 16

Abstract

Abstract CK-666 (1) is a recently discovered small-molecule inhibitor of the actin-related protein 2/3 (Arp2/3) complex, a key actin cytoskeleton regulator with roles in bacterial pathogenesis and cancer cell motility. Although 1 is commercially available, the crystal structure of Arp2/3 complex with 1 bound has not been reported, making its mechanism of action uncertain. Furthermore, its relatively low potency increases its potential for off-target ...