PF-03758309 (hydrochloride)

PF-3758309 (PF-03758309) hydrochloride is a potent, orally available, and reversible ATP-competitive inhibitor of PAK4 (Kd= 2.7 nM; Ki=18.7 nM). PF-3758309 hydrochloride 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].

PAK4: 18.7 nM (Ki); PAK1: 13.7 nM (Ki); PAK5: 18.1 nM (Ki); PAK6: 17.1 nM (Ki); PAK2: 190 nM (IC₅₀); PAK3: 99 nM (IC₅₀); PAK4: 2.7 nM (Kd)

[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. DOI:10.1073/pnas.0911863107
[2] Zhao ZS, et al. Do PAKs make good drug targets F1000 Biol Rep. 2010 Sep 23;2:70. DOI:10.3410/B2-70
[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. DOI:10.1007/s11010-013-1928-8