G-5555 hydrochloride是有效，选择性的PAK1抑制剂，Ki值为3.7 nM。

G-5555 hydrochloride is a potent and selective p21-activated kinase 1 ( PAK1 ) inhibitor with a K i of 3.7 nM.

G-5555 shows excellent kinase selectivity and inhibits only eight out of the 235 kinases tested other than PAK1 with inhibition >70%: PAK2, PAK3, KHS1, Lck, MST3, MST4, SIK2, and YSK1. The IC 50 s of G-5555 against SIK2, PAK2, KHS1, MST4, YSK1, MST3 and Lck are 9, 11, 10, 20, 34, 43, 52 nM, respectively. In general, G-5555 demonstrates high selectivity for the group I PAKs. There is negligible activity for G-5555 against the hERG channel with IC 50 more than 10 μM in a patch clamp assay [1]. In an array of 23 breast cancer cell lines, G-5555 has significantly greater growth inhibitory activity in cell lines that are PAK-amplified compared to non-amplified lines [2].

G-5555 exhibits low blood clearance and an acceptable half-life. Good oral exposure (AUC=30 μM h) and high oral bioavailability (F=80%) are achieved [1]. In an H292 non-small cell lunger cancer (NSCLC) xenograft study in mice, G-5555 inhibits phosphorylation of the PAK1/2 downstream substrate mitogen-activated protein kinase 1 (MEK1) S298 and, when administered at an oral dose of 25 mg/kg b.i.d., imparts 60% tumor growth inhibition in this model13 and a PAK1 amplified breast cancer xenograft model, MDAMB-175 [2].

C25H26Cl2N6O3

529.42

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years