Cell-active small molecule inhibitors validate the SNM1A DNA repair nuclease as a cancer target

Author:

Bielinski Marcin1ORCID,Henderson Lucy R.2ORCID,Yosaatmadja Yuliana3,Swift Lonnie P.2,Baddock Hannah T.2,Bowen Matthew J.1ORCID,Brem Jürgen1ORCID,Jones Philip S.4,McElroy Stuart P.4,Morrison Angus4,Speake Michael4ORCID,van Boeckel Stan5,van Doornmalen Els5,van Groningen Jan5,van den Hurk Helma5,Gileadi Opher3ORCID,Newman Joseph A.3,McHugh Peter J.2ORCID,Schofield Christopher J.1ORCID

Affiliation:

1. Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute for Antimicrobial Research, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK

2. Department of Oncology, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK

3. Centre for Medicines Discovery, NDM Research Building, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK

4. University of Dundee, European Screening Centre, Newhouse, ML1 5UH, UK

5. Pivot Park Screening Centre, 5349 AB Oss, The Netherlands

Abstract

SNM1 metallo-β-lactamase fold nucleases (human SNM1A–C) play roles in DNA damage repair and telomere maintenance. Screening and SAR studies lead to selective small molecules validating SNM1A as a cancer target.

Funder

Cancer Research UK

European Federation of Pharmaceutical Industries and Associations

Innovative Medicines Initiative

Seventh Framework Programme

Publisher

Royal Society of Chemistry (RSC)

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