The Selectivity of Butyrylcholinesterase Inhibitors Revisited

  • Molecules. 2025 Oct 27;30(21):4201. doi: 10.3390/molecules30214201.
Michael D Gambardella  1  2 ,  Yigui Wang  2  3 ,  Jiongdong Pang  2
Affiliations
  • 1. Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
  • 2. Department of Chemistry and Biochemistry, Southern Connecticut State University, New Haven, CT 06515, USA.
  • 3. Department of Chemistry and Chemical & Biochemical Engineering, University of New Haven, West Haven, CT 06516, USA.
PMID: 41226162 DOI: 10.3390/molecules30214201
Abstract

Acetylcholinesterase (AChE) inhibitors are the primary target for single-molecule anti-Alzheimer's disease (AD) therapeutics. Though AChE has historically been the focus of investigation for small-molecule inhibitors, interest in another cholinergic enzyme, butyrylcholinesterase (BChE), has grown in recent years. Attention stems from BChE's role in β-amyloid (Aβ) protein aggregation and an increase in BChE concentration during the late stages of AD, where a decrease in AChE concentration is also observed. Currently, five FDA-approved drugs are on the market for inhibiting AChE, though no BChE-selective drugs have been approved so far. In this review, we focus on newly identified BChE selective inhibitors and present the ideas behind these discoveries.

Keywords
Alzheimer’s disease; BChE selectivity; acetylcholinesterase; butyrylcholinesterase; inhibitor; synthesis; virtual screening.
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