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

Bingyan Li; Kang Yang; Dailin Liang; Cheng Jiang; Zonghui Ma

doi:10.1016/j.ejmech.2020.112940

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

Eur J Med Chem. 2021 Jan 1:209:112940. doi: 10.1016/j.ejmech.2020.112940. Epub 2020 Oct 17.

Authors

Bingyan Li¹, Kang Yang², Dailin Liang¹, Cheng Jiang³, Zonghui Ma⁴

Affiliations

¹ Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Tongjiaxiang 24, Nanjing, 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Tongjiaxiang 24, Nanjing, 210009, China.
² Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang 24, Nanjing, 210009, China.
³ Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Tongjiaxiang 24, Nanjing, 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Tongjiaxiang 24, Nanjing, 210009, China. Electronic address: jc@cpu.edu.cn.
⁴ Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Tongjiaxiang 24, Nanjing, 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Tongjiaxiang 24, Nanjing, 210009, China. Electronic address: zonghuima@cpu.edu.cn.

PMID: 33328099
DOI: 10.1016/j.ejmech.2020.112940

Abstract

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.

Keywords: ALDH1A1; ALDHs; Aldehydes metabolization; Chemical tools; Inhibitors; Selectivity.

Publication types

Review

MeSH terms

Aldehyde Dehydrogenase 1 Family / antagonists & inhibitors*
Drug Discovery*
Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Enzyme Inhibitors / therapeutic use
Humans
Retinal Dehydrogenase / antagonists & inhibitors*

Substances

Enzyme Inhibitors
Aldehyde Dehydrogenase 1 Family
ALDH1A1 protein, human
Retinal Dehydrogenase