NVS-PAK1-1 is a potent allosteric inhibitor of p21-activated kinase PAK1, a serine-threonine kinase that is upregulated in many cancers. NVS-PAK1-1 has an IC50 value of 5 nM for dephoshorylated PAK1 and 6 nM for phosphorylated PAK1 in an in vitro dephosphorylation assay.
PAK1 is a serine/threonine protein kinase involved in cytoskeletal signaling and oncogenic transformation. The dysregulation of PAK1 has been reported in breast, squamous NSCLC, and pancreatic cancers. NVS-PAK1-1 is a potent, selective, allosteric PAK1 Inhibitor with an IC50 value of 5nM. It has a biochemical PAK1 Kd of 7nM and a PAK2 Kd of 400nM. NVS-PAK1-1 significantly inhibited pMEK Ser289 at a concentration of 6–20μM. It inhibited the proliferation of Su86.86 cells at a concentration of 2μM. NVS-PAK1-1 at 0.21μM also significantly inhibited downstream signaling and cell proliferation when applied together with PAK2 shRNA. NVS-PAK1-1 exhibited high Caco2 permeability (Papp A-B 42.8 × 10-8cm/s). NVS-PAK1-1 showed a relatively poor stability in rat liver microsomes (t1/2=3.5min)[2].
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