FRAX597

FRAX597 is a small molecule pyridopyrimidinone inhibitor that acts as a potent, ATP-competitive inhibitor of group I p21-activated kinases (PAKs), specifically targeting PAK1, PAK2, and PAK3[1][2][3][7]. It was discovered through structure-activity relationship optimization following high-throughput screening for PAK inhibitors[1]. FRAX597 demonstrates nanomolar inhibitory potency in biochemical assays (PAK1 IC50 = 8 nM, PAK2 IC50 = 13 nM, PAK3 IC50 = 19 nM), with strong selectivity over group II PAKs[1][3][9]. Its mechanism involves binding to the ATP site of target kinases, leading to G1 cell cycle arrest in tumor cells without impacting cell viability[1][3]. FRAX597 has shown potent anti-tumor activity in vitro and in vivo, including models of neurofibromatosis type 2 (NF2)-associated schwannomas and several pancreatic cancer cell lines[1][2][5][6]. It displays synergistic anti-proliferative effects in combination with other chemotherapeutics (e.g., gemcitabine) and enhances chemosensitivity in preclinical cancer models[5][4]. The compound is used primarily in research, with no evidence of clinical development or commercialization.

Other names

FRAX597FRAX-597FRAX 597