| 生化机理 |
Description:
IC50 Value: 2.5uM; 1.92 ± 0.2 μM( Dissociation constant) [1]
IPA-3 is a novel small-molecule PAK inhibitor. IPA-3 binds covalently to the Pak1 regulatory domain and prevents binding to the upstream activator Cdc42.
in vitro: Saturable binding of IPA-3 to full-length Pak1 was observed with an apparent dissociation constant of 1.92 ± 0.2 μM, consistent with the reported IC50 of 2.5 μM. IPA-3 bound the isolated RD with an even higher apparent affinity (0.1 ± 0.01 μM) whereas the kinase domain showed a weaker interaction. IPA-3 blocks activation of PAK2 at Ser192/197 that antagonises PAK's interaction with Pix. Accordingly, Pix-mediated Rac1 activation is decreased in IPA-3 treated schwannoma cells, indicating that PAK acts upstream of Rac [2]. In K562 cells, both chorein silencing and PAK1 inhibition with IPA-3 decreased phosphorylation of Bad, a Bcl2-associated protein, promoting apoptosis by forming |
