Uses

p21-activated kinases (Paks) are serine/threonine protein kinases involved in cellular signaling pathways. PAK1 is an effector of Rho GTPase. PAKs are oncogenic kinases, which have been implicated as potential therapeutic targets. FRAX 597 is a PAK1 inhibitor that can reduce pancreatic cancer growth when used with Gemcitabine (G305000), an antineoplastic agent.

Biological Activity

frax597 is a small-molecule inhibitor of the group 1 p21-activated kinases (paks) with ic50 values of 8nm, 13nm and 19nm, respectively for pak1, pak2 and pak3 [1].the paks family includes two sub groups: 1 and 2. these kinases take participate in the growth of various types of cancers. frax597 is developed to be an inhibitor of group 1 paks from the initial hits of a high throughput screen. it is an atp-competitive inhibitor of pak 1-3. to group 2 paks, frax597 shows minimal inhibitory activity. the inhibition mechanism of frax597 is that it binds pak by targeting the atp binding site and competes with atp. frax597 is reported to suppress cell proliferation by arresting cell cycle in g1 without impacting cell viability in schwann cells. in vivo assay also demonstrates frax597 can suppress tumor growth in an orthotopic model of nf2. this effect on the cells has been proved to be mediated through the inhibition of the group i paks [1].

in vivo

target

PAK1

IC 50

PAK1: 8 nM (IC₅₀); PAK2: 13 nM (IC₅₀); PAK3: 19 nM (IC₅₀)

storage

Store at -20°C

References

[1] silvia licciulli, jasna maksimoska, chun zhou, scott troutman, smitha kota, qin liu, sergio duron, david campbell, jonathan chernoff, jeffery field, ronen marmorstein and joseph l. kissil. frax597, a small molecule inhibitor of the p21-activated kinases, inhibits schwannomas tumorigenesis of nf2-associated. j. biol. chem. 2013, august.