Small molecules that allosterically inhibit p21-activated kinase activity by binding to the regulatory p21-binding domain.
- Author:
Duk Joong KIM
1
;
Chang Ki CHOI
;
Chan Soo LEE
;
Mee Hee PARK
;
Xizhe TIAN
;
Nam Doo KIM
;
Kee In LEE
;
Joong Kwon CHOI
;
Jin Hee AHN
;
Eun Young SHIN
;
Injae SHIN
;
Eung Gook KIM
Author Information
- Publication Type:Original Article
- MeSH: Actins; Cell Proliferation; Cell Survival; Humans; In Vitro Techniques; Mass Screening; Nervous System Diseases; p21-Activated Kinases; Phosphotransferases*; rho GTP-Binding Proteins
- From:Experimental & Molecular Medicine 2016;48(4):e229-
- CountryRepublic of Korea
- Language:English
- Abstract: p21-activated kinases (PAKs) are key regulators of actin dynamics, cell proliferation and cell survival. Deregulation of PAK activity contributes to the pathogenesis of various human diseases, including cancer and neurological disorders. Using an ELISA-based screening protocol, we identified naphtho(hydro)quinone-based small molecules that allosterically inhibit PAK activity. These molecules interfere with the interactions between the p21-binding domain (PBD) of PAK1 and Rho GTPases by binding to the PBD. Importantly, they inhibit the activity of full-length PAKs and are selective for PAK1 and PAK3 in vitro and in living cells. These compounds may potentially be useful for determining the details of the PAK signaling pathway and may also be used as lead molecules in the development of more selective and potent PAK inhibitors.
