ArticleScientific reports2019
The small molecule inhibitor anle145c thermodynamically traps human islet amyloid peptide in the form of non-cytotoxic oligomers.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 29 citations in OpenAlex.
- Molecular Mechanisms of Islet Amyloid Polypeptide Aggregation: Towards Chemical Strategies to Prevent Amyloid Formation and to Design Non-Aggregating Peptide Therapeutics.International journal of molecular sciences · 2026Review
- Anle138b binds predominantly to the central cavity in lipidic Aβ₄₀ fibrils and modulates fibril formation.Nature communications · 2025Article
- Monomer binding modes of small molecules that modulate the kinetics of hIAPP amyloid formation.bioRxiv : the preprint server for biology · 2025Article
- Human IAPP is a contributor to painful diabetic peripheral neuropathy.The Journal of clinical investigation · 2023Article
- It's ok to be outnumbered - sub-stoichiometric modulation of homomeric protein complexes.RSC medicinal chemistry · 2023Review
- Controlling amyloid formation of intrinsically disordered proteins and peptides: slowing down or speeding up?Essays in biochemistry · 2022Article
- Human islet amyloid polypeptide: A therapeutic target for the management of type 2 diabetes mellitus.Journal of pharmaceutical analysis · 2022Review
- Tuning the rate of aggregation of hIAPP into amyloid using small-molecule modulators of assembly.Nature communications · 2022Article
- β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances.Metabolites · 2021Review
- Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.Chemical reviews · 2021Review
- β-Hairpin Peptide Mimics Decrease Human Islet Amyloid Polypeptide (hIAPP) Aggregation.Frontiers in cell and developmental biology · 2021Article
- Sub-stoichiometric inhibition of IAPP aggregation: a peptidomimetic approach to anti-amyloid agents.RSC chemical biology · 2020Article
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Authors and funding
10 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 2 diabetes (T2DM) is associated with aggregation of the human islet amyloid polypeptide (hIAPP) into cytotoxic amyloid species. Here we tested the effect of a diphenylpyrazole (DPP)-derived small molecule inhibitor, anle145c, on cytotoxicity and on aggregation properties of hIAPP. We demonstrate that incubation of hIAPP with the inhibitor yields ~10 nm-sized non-toxic oligomers, independent of the initial aggregation state of hIAPP. This suggests that anle145c has a special mode of action in which anle145c-stabilized oligomers act as a thermodynamic sink for the preferred aggregation state of hIAPP and anle145c. We also demonstrate that the inhibitor acts in a very efficient manner, with sub-stoichiometric concentrations of anle145c being sufficient to (i) inhibit hIAPP-induced death of INS-1E cells, (ii) prevent hIAPP fibril formation in solution, and (iii) convert preformed hIAPP fibrils into non-toxic oligomers. Together, these results indicate that anle145c is a promising candidate for inhibition of amyloid formation in T2DM.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.