Computational and experimental approaches to design inhibitors of amylin aggregation

Ammu Prasanna Kumar, Sungmun Lee, Suryani Lukman

Research output: Contribution to journalShort surveypeer-review

1 Scopus citations


Amylin is a neuroendocrine peptide hormone secreted by pancreatic ß-cells; however, amylin is toxic to ß-cells when it is aggregated in type 2 diabetes mellitus (T2DM). It is important to understand amylin’s structures and aggregation mechanism for the discovery and design of effective drugs to inhibit amylin aggregation. In this review, we investigated experimental and computational studies on amylin structures and inhibitors. Our review provides some novel insights into amylin, particularly for the design of its aggregation inhibitors to treat T2DM. We detailed the potential inhibitors that have been studied hitherto and highlighted the neglected need to consider different amylin attributes that depend on the presence/absence of physiologically relevant conditions, such as membranes. These conditions and the experimental methods can greatly influence the results of studies on amylin-inhibitor complexes. Text-mining over 3,000 amylin-related PubMed abstracts suggests the combined therapeutic potential of amylin with leptin and glucagon-like peptide-1, which are two key hormones in obesity. The results also suggest that targeting amylin aggregation can contribute to therapeutic efforts for Alzheimer’s disease (AD). Therefore, we have also reviewed the role of amylin in other conditions including obesity and AD. Finally, we provided insights for designing inhibitors of different types (small molecules, proteins, peptides/mimetics, metal ions) to inhibit amylin aggregation.

Original languageBritish English
Pages (from-to)1680-1694
Number of pages15
JournalCurrent Drug Targets
Issue number16
StatePublished - 2019


  • Aggregation inhibitors
  • Alzheimer's disease therapy
  • Amylin
  • Conformation of amylin
  • IAPP
  • Islet amyloid polypeptide
  • Literature review
  • Type 2 diabetes therapy


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