Ayotte, Yann, Bernet, Eve, Bilodeau, François, Cimino, Mena, Gagnon, Dominic, Lebughe, Marthe, Mistretta, Maxime, Ogadinma, Paul, Ouali, Sarah-Lisa, Sow, Aïssatou Aïcha, Chatel-Chaix, Laurent 
ORCID: https://orcid.org/0000-0002-7390-8250, Descoteaux, Albert ORCID: https://orcid.org/0000-0002-0633-5309, Manina, Giulia, Richard, Dave, Veyrier, Frédéric ORCID: https://orcid.org/0000-0002-8574-0547 et Laplante, Steven ORCID: https://orcid.org/0000-0003-2835-5789
(2021).
Fragment-Based Phenotypic Lead Discovery To Identify New Drug Seeds That Target Infectious Diseases
ACS Chemical Biology
, vol. 16
, nº 11.
p. 2158-2163.
DOI: 10.1021/acschembio.1c00657.
Résumé
Fragment-based lead discovery has emerged over the last decades as one of the most powerful techniques for identifying starting chemical matter to target specific proteins or nucleic acids in vitro. However, the use of such low-molecular-weight fragment molecules in cell-based phenotypic assays has been historically avoided because of concerns that bioassays would be insufficiently sensitive to detect the limited potency expected for such small molecules and that the high concentrations required would likely implicate undesirable artifacts. Herein, we applied phenotype cell-based screens using a curated fragment library to identify inhibitors against a range of pathogens including Leishmania, Plasmodium falciparum, Neisseria, Mycobacterium, and flaviviruses. This proof-of-concept shows that fragment-based phenotypic lead discovery (FPLD) can serve as a promising complementary approach for tackling infectious diseases and other drug-discovery programs.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | - |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 22 juin 2022 19:09 |
| Dernière modification: | 22 juin 2022 19:09 |
| URI: | https://espace.inrs.ca/id/eprint/12286 |
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