NVS-PAK1-1

NVS-PAK1-1 is a potent and selective allosteric PAK1 inhibitor with an IC₅₀ of 5 nM. IC50 & Target: IC50: 5 nM (PAK1)^[1] In Vitro: NVS-PAK1-1 demonstrates high selectivity for inhibition of PAK1 over other PAK isoforms and the kinome in general. NVS-PAK1-1 has a biochemical PAK1 K_d of 7 nM and a PAK2 K_d of 400 nM. NVS-PAK1-1 shows excellent activity in biochemical assays and an exceptional selectivity profile against other known kinases. NVS-PAK1-1 at 6-20 μM inhibits the phosphorylation of the downstream substrate MEK1 Ser289. Consistent with the observation, NVS-PAK1-1 inhibits proliferation of Su86.86 cell line only above a concentration of 2 μM. In contrast, by applying a mixture of NVS-PAK1-1 and PAK2 shRNA, inhibition of downstream signaling and cell proliferation at a significantly lower 0.21 μM concentration are achieved^[1]. In Vivo: NVS-PAK1-1 shows a relatively poor stability in rat liver microsomes (RLM) and this would limit its application for in vivo studies (t_1/2 in RLM 3.5 min)^[1].