PF-3758309 dihydrochloride  (Synonyms: PF-03758309 dihydrochloride)

PF-3758309 (PF-03758309) dihydrochloride is a potent, orally available, and reversible ATP-competitive inhibitor of PAK4 (K_d= 2.7 nM; K_i=18.7 nM). PF-3758309 dihydrochloride has the expected cellular functions of a PAK4 inhibitor: inhibition of anchorage-independent growth, induction of apoptosis, 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

563.55

C₂₅H₃₂Cl₂N₈OS

CC1=NC2=C(SC=C2)C(NC3=NNC4=C3CN(C(N[C@@H](C5=CC=CC=C5)CN(C)C)=O)C4(C)C)=N1.[H]Cl.[H]Cl

Room temperature in continental US; may vary elsewhere.

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

• [1]. Murray, Brion W., et al. Small-molecule p21-activated kinase inhibitor PF3758309 is a potent inhibitor of oncogenic signaling and tumor growth. Proceedings of the National Academy of Sciences of the United States of America (2010), 107(20), 9446-9451, S94  [Content Brief]

  [2]. Zhao ZS, et al. Do PAKs make good drug targets? F1000 Biol Rep. 2010 Sep 23;2:70.  [Content Brief]

  [3]. Ryu BJ, et al. PF-3758309, p21-activated kinase 4 inhibitor, suppresses migration and invasion of A549 human lung cancer cells via regulation of CREB, NF-κB, and β-catenin signalings. Mol Cell Biochem. 2014 Apr;389(1-2):69-77.  [Content Brief]