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However, the discovery of therapeutic agents has been immensely challenging largely because of (i) the diverse number of aggregation pathways and the multi-conformational and transient nature of the related proteins or peptides and (ii) the under-development of experimental pipelines for the identification of disease-modifying molecules and their mode-of-action. Here, we describe current approaches used in the search for small-molecule modulators able to control or arrest amyloid formation commencing from IDPs and review recently reported accelerators and inhibitors of amyloid formation for this class of proteins. We compare their targets, mode-of-action and effects on amyloid-associated cytotoxicity. Recent successes in the control of IDP-associated amyloid formation using small molecules highlight exciting possibilities for future intervention in protein-misfolding diseases, despite the challenges of targeting these highly dynamic precursors of amyloid assembly.<\/jats:p>","DOI":"10.1042\/ebc20220046","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T10:49:31Z","timestamp":1660733371000},"page":"959-975","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Controlling amyloid formation of intrinsically disordered proteins and peptides: slowing down or speeding up?"],"prefix":"10.1042","volume":"66","author":[{"given":"Yong","family":"Xu","sequence":"additional","affiliation":[{"name":"Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, LS2 9JT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Maya-Martinez","sequence":"additional","affiliation":[{"name":"Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, LS2 9JT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3079-8039","authenticated-orcid":false,"given":"Sheena\u00a0E.","family":"Radford","sequence":"additional","affiliation":[{"name":"Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, LS2 9JT, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"2022121609084772600_B1","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1038\/s41580-018-0060-8","article-title":"A new era for understanding amyloid structures and disease","volume":"19","author":"Iadanza","year":"2018","journal-title":"Nat. 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