AAA-237

AAA-237 is a novel small molecule inhibitor that targets S-phase kinase-associated protein 2 (Skp2), an oncogenic E3 ubiquitin ligase implicated in the progression of various cancers. By binding to Skp2, AAA-237 inhibits its activity and disrupts the degradation of cell cycle inhibitors p21Cip1 and p27Kip1, leading to cell cycle arrest at the G0/G1 phase. In non-small cell lung cancer (NSCLC) models, it induces apoptosis and senescence in a dose-dependent manner. In glioblastoma models, AAA-237 suppresses tumor growth by upregulating BNIP3 and inducing BNIP3-dependent autophagy through modulation of the mTOR pathway. Preclinical studies also show efficacy against Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), where it triggers pyroptosis via mitochondrial dysfunction. These findings suggest that AAA-237 may be a promising therapeutic candidate for multiple malignancies including NSCLC, glioblastoma, and Ph+ ALL[1][3][5][6].