Screening of the ‘Open Scaffolds’ collection from Compounds Australia identifies a new chemical entity with anthelmintic activities against different developmental stages of the barber's pole worm and other parasitic nematodes

S Preston; Y Jiao; JB Baell; J Keiser; S Crawford; AV Koehler; T Wang; MM Simpson; RM Kaplan; KJ Cowley; KJ Simpson; A Hofmann; A Jabbar; RB Gasser

Journal article

Screening of the ‘Open Scaffolds’ collection from Compounds Australia identifies a new chemical entity with anthelmintic activities against different developmental stages of the barber's pole worm and other parasitic nematodes

S Preston, Y Jiao, JB Baell, J Keiser, S Crawford, AV Koehler, T Wang, MM Simpson, RM Kaplan, KJ Cowley, KJ Simpson, A Hofmann, A Jabbar, RB Gasser

International Journal for Parasitology Drugs and Drug Resistance | ELSEVIER SCI LTD | Published : 2017

DOI: 10.1016/j.ijpddr.2017.05.004

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Abstract

The discovery and development of novel anthelmintic classes is essential to sustain the control of socioeconomically important parasitic worms of humans and animals. With the aim of offering novel, lead-like scaffolds for drug discovery, Compounds Australia released the ‘Open Scaffolds’ collection containing 33,999 compounds, with extensive information available on the physicochemical properties of these chemicals. In the present study, we screened 14,464 prioritised compounds from the ‘Open Scaffolds’ collection against the exsheathed third-stage larvae (xL3s) of Haemonchus contortus using recently developed whole-organism screening assays. We identified a hit compound, called SN00797439, w..

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University of Melbourne Researchers

Anson Koehler Author

Tao Wang Author

Kaylene Simpson Author

Andreas Hofmann Author

Grants

Awarded by Australian Research Council

Funding Acknowledgements

The present study was funded by the National Health and Medical Research Council of Australia (NHMRC), the Australian Research Council (ARC) and the Wellcome Trust (RBG), and supported by a Victoria Life Sciences Computation Initiative, Australia (VLSCI; grant no. VR0007) on its Peak Computing Facility at The University of Melbourne, Australia, an initiative of the Victorian Government, Australia. Animal ethics approval (AEC no. 0707258) was granted by The University of Melbourne. We thank our colleagues at Medicines for Malaria Ventures (MMV) for their support. We expressly wish to acknowledge the efforts of the constructors of the 'Open Scaffold' library at Compounds Australia, David Camp, Graeme Stevenson, Mikhail Krasavin and Alain-Dominique Gorse. The Victorian Centre for Functional Genomics (KJS) is supported by funding from the Australian Government's Education Investment Fund through the Super Science Initiative and the Peter MacCallum Cancer Centre Foundation. We thank an anonymous reviewer for constructive comments and suggestions on our manuscript.