PF-3758309 (PF-03758309) dihydrochloride is a potent, orally available, and reversible ATP-competitive inhibitor ofPAK4(K_d= 2.7 nM;K_i=18.7 nM). PF-3758309 dihydrochloride has the expected cellular functions of aPAK4inhibitor: inhibition of anchorage-independent growth, induction ofapoptosis, cytoskeletal remodeling, and inhibition of proliferation^[1][2][3].

PF-3758309 dihydrochloride has similar enzymatic potency against the kinase domains of the other group B PAKs (PAK5, K_i=18.1 nM; PAK6, K_i=17.1 nM) and group A PAK1 (K_i=13.7 nM), but is less active against the other two group A PAKs (PAK2, IC₅₀=190 nM; PAK3, IC₅₀=99 nM)^[1].
In cells, PF-3758309 dihydrochloride inhibits phosphorylation of the PAK4 substrate GEF-H1 (IC₅₀=1.3 nM) and anchorage-independent growth of a panel of tumor cell lines (IC₅₀=4.7 nM)^[1].
PF-3758309 dihydrochloride also inhibits endogenous pGEF-H1 accumulation in HCT116 cells. PF-3758309 potently inhibits cellular proliferation (IC₅₀=20 nM) and anchorage-independent growth (IC₅₀=27 nM) of A549 cells^[1].

PF-3758309 dihydrochloride (7.5-30 mg/kg; p.o.; twice daily for 9-18 days) results in statistically significant tumor growth inhibition (TGI) in HCT116 and A549 models^[1].

563.55

C₂₅H₃₂Cl₂N₈OS

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.