Discovery and development of selective aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors

ALDH1A1, one important member of 19 ALDHs, can metabolize reactive aldehydes to their corresponding carboxylic acid derivatives and play important physiological and toxicological roles in many areas, including CNS, metabolic disorders, and cancers. Overexpression of ALDH1A1 correlates with poor prognosis and tumor aggressiveness, is associated with drug resistance in traditional chemotherapy for cancer treatment and contributes to obesity, diabetes, and inflammation. So, inhibition of ALDH1A1 may offer new therapeutic options for patients with cancer, obesity, diabetes, and inflammation. Up to now, many ALDH1A1 inhibitors with different scaffolds have been identified and developed as useful chemical tools for better understanding of the functions of ALDH1A1 in physiologic and pathophysiologic conditions. In this review, the advances in the discovery and development of selective ALDH1A1 inhibitors are summarized, and opportunities and challenges associated with this field are also discussed. [Display omitted] •ALDH1A1 can metabolize reactive aldehydes to carboxylic acid derivatives to alleviate aldehyde stress.•ALDH1A1 plays important physiological and toxicological roles in many areas, including CNS, metabolic disorders, and cancers.•Inhibition of ALDH1A1 offers new therapeutic options for patients with cancer, obesity, diabetes and so on.•This review summarized the recent advances of selective ALDH1A1 inhibitors.