This is a repository copy of An in vivo platform for identifying inhibitors of protein aggregation.

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1 This is a repository copy of An in vivo platform for identifying inhibitors of protein aggregation. White Rose Research Online URL for this paper: Version: Supplemental Material Article: Saunders, JC, Young, LM, Mahood, RA et al. (7 more authors) (2016) An in vivo platform for identifying inhibitors of protein aggregation. Nature Chemical Biology, 12 (2). pp ISSN Reuse Unless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version - refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher s website. Takedown If you consider content in White Rose Research Online to be in breach of UK law, please notify us by ing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. eprints@whiterose.ac.uk

2 An in vivo platform for identifying inhibitors of protein aggregation Janet C. Saunders 1, 2, Lydia M. Young 1, 2, Rachel A. Mahood 1, 2, Matthew P. Jackson 1, 2, Charlotte H. Revill 1, 3, Richard J. Foster 1, 3, D. Alastair Smith 4, Alison E. Ashcroft 1, 2, David J. Brockwell 1, 2 *, Sheena E. Radford 1, 2 * These authors contributed equally to this work *Corresponding authors: D.J.Brockwell@leeds.ac.uk and S.E.Radford@leeds.ac.uk 1 Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK. 2 School of Molecular and Cellular Biology, University of Leeds, Leeds, LS2 9JT, UK. 3 School of Chemistry, University of Leeds, LS2 9JT, UK. 4 Avacta Analytical plc, Wetherby, LS23 7FZ, UK Supplementary Dataset 1 contains a full list of all small molecules used in this study and their structures and chemical properties.

3 Supplementary Data Set 1. Structure and properties of small molecules. Hit compounds from the in vivo screen are highlighted in pink. LogP values (the log of the aqueous/hydrophobic partition coefficient) were calculated using software, which determines the hydrophobic properties of the substituents. Molecules with high positive LogP values have high hydrophobicity. PAINS key: [functional group or substructure] followed by possible mechanism of action of PAINS (determined by historical analysis of PAINS filters 21, 22 ). No = molecule with absence of PAINS substructure. Note: it is not always possible to allocate a specific functional group or substructure to the PAINS.

4 always possible to allocate a specific functional group or substructure to the PAINS.

5 always possible to allocate a specific functional group or substructure to the PAINS.

6 historical analysis of PAINS filters 21, 22 ). No = molecule with absence of PAINS substructure. JCS-1 contains a sub-structural class (carboxypyrimidinone) which although is not specified as problematic by the Baell 2010 PAINS filters 21, is structurally related to the cyanopyridone group, which is a PAINS.

7 always possible to allocate a specific functional group or substructure to the PAINS.

8 always possible to allocate a specific functional group or substructure to the PAINS.

9 always possible to allocate a specific functional group or substructure to the PAINS.

10 always possible to allocate a specific functional group or substructure to the PAINS.

11 always possible to allocate a specific functional group or substructure to the PAINS. Compounds contain a sub-structural class (carboxypyrimidinone) which although is not specified as problematic by the Baell 2010 PAINS filters 21, is structurally related to the cyanopyridone group, which is a PAINS.

12 always possible to allocate a specific functional group or substructure to the PAINS. Compounds contain a sub-structural class (carboxypyrimidinone) which although is not specified as problematic by the Baell 2010 PAINS filters 21, is structurally related to the cyanopyridone group, which is a PAINS.

13 always possible to allocate a specific functional group or substructure to the PAINS. Compounds contain a sub-structural class (carboxypyrimidinone) which although is not specified as problematic by the Baell 2010 PAINS filters 21, is structurally related to the cyanopyridone group, which is a PAINS.