CB29

CB29 is a selective small-molecule inhibitor of human aldehyde dehydrogenase 3A1 (ALDH3A1). ALDH3A1 is an enzyme that plays a significant role in cellular oxidative processes and is frequently overexpressed in various cancers, including lung adenocarcinoma and glioblastoma, where it contributes to chemoresistance by metabolizing oxazaphosphorine drugs such as cyclophosphamide and its analogues. CB29 works by binding within the aldehyde substrate-binding site of the ALDH3A1 isoenzyme, thereby blocking its activity. While CB29 does not show independent anti-proliferative effects on cancer cells, it has been demonstrated to enhance the cytotoxicity of mafosfamide in ALDH3A1-expressing tumor cell lines. It exhibits high selectivity for ALDH3A1, showing no significant inhibition of other ALDH isoenzymes like ALDH1A1, ALDH1A2, ALDH1A3, ALDH1B1, or ALDH2 at concentrations up to 250 μM.