The Arp2/3 complex consists of seven evolutionarily conserved subunits (Arp2, Arp3 and ARPC1-5) and plays an essential role in polymerization of actin filaments which supports many types of cellular movements[3]. CK-636 is a inhibitor of Arp2/3 complex which could inhibit actin polymerization stimulated by Arp2/3 complex with IC50 values of 4 μM, 24 μM and 32 μM for human, fission yeast and bovine, respectively[3]. By the THP-1 monocyte cell line, CK-636 inhibited the formation of podosomes which are adhesive structures depending on Arp2/3 complex, WASP (Wiskott–Aldrich syndrome protein) and actin polymerization[3]. When the formation of lamellipodia was inhibited by CK-636, a substantial fraction of T cells on those surfaces containing zigzag patterns with an acute turning angle were trapped at the interfaces formed by the turning points of the zigzag patterns[4].
作用机制
CK-636 binds in a pocket between subdomain 4 of Arp2 and subdomain 1 of Arp3.
Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):E3820-9.
SKOV3 cells
100 μM
60 minutes
Inhibition of actin filament comet tail formation by Listeria monocytogenes
Nature. 2009 Aug 20;460(7258):1031-4.
T cells
50 μM
Inhibition of Arp2/3, reducing lamellipodia formation at the leading edges of T cells, resulting in decreased migration speed on complex nanotopographical surfaces
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