Description
General description
G-5555 is a selective p21-activated kinase (PAK1) inhibitor. In addition to this it also selectively inhibits eight kinases such as PAK2, PAK3, KHS1, lymphocyte-specific protein tyrosine kinase (LcK), Mammalian Ste20-like kinase 3 (MST3), Mammalian Ste20-like kinase 4 (MST4), salt-inducible kinase 2(SIK2), and Yeast Sps1/Ste20-related Kinase 1 (YSK1). G-5555 exhibits high stability and low human ether-à-go-go related gene (hERG) activity than other PAK inhibitors including FRAX1036.
Biochem/physiol Actions
ATP site-targeting inhibitor against SIK1/2/3, MST3/4, PAK1/2, YANK1/3, MAP2K5 and MAP4K5. Reduces cellular MEK pS298 in cultures and in mice in vivo.
G-5555 is an ATP site-targeting inhibitor against salt-inducible kinases, MST3/4, p21-activated kinase 1/2, YANK1/3, MAP2K5, MAP4K5 (% inhibition at 100 nM = 98.6/93.5/99.8 (SIK1/2/3), 85/99.5 (MST3/4), 95.6/87 (PAK1/2), 94.7/96.5 (YANK1/3); 87/MAP2K5, 83/MAP4K5) with good selectivity over other kinases. G-5555 downregulates MEK pS298 in EBC1 cells in cultures (IC50 = 69 nM) and in H292 NSCLC tumors in mice in vivo (25 mg/kg p.o.) with good oral availability (mice F = 80%, monkeys F = 72%).
G-5555 is an ATP site-targeting inhibitor against salt-inducible kinases, MST3/4, p21-activated kinase 1/2, YANK1/3, MAP2K5, MAP4K5 (% inhibition at 100 nM = 98.6/93.5/99.8 (SIK1/2/3), 85/99.5 (MST3/4), 95.6/87 (PAK1/2), 94.7/96.5 (YANK1/3); 87/MAP2K5, 83/MAP4K5) with good selectivity over other kinases. G-5555 downregulates MEK pS298 in EBC1 cells in cultures (IC50 = 69 nM) and in H292 NSCLC tumors in mice in vivo (25 mg/kg p.o.) with good oral availability (mice F = 80%, monkeys F = 72%). PAK1 plays a crucial role in cancer progression, inhibiting this protein has the potential to reduce cancer development. Therefore, G-5555 may be a promising candidate for oncology research.
