Academic Journal
FRET prioritization score to choose high-quality hit equity and reduce the impact of interference by quenching and fluorescence.
| Τίτλος: | FRET prioritization score to choose high-quality hit equity and reduce the impact of interference by quenching and fluorescence. |
|---|---|
| Συγγραφείς: | Turberville A; Hit Discovery, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UK., Monteverde T; Hit Discovery, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UK., Ashraf SN; Hit Discovery, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UK., Ivanov D; Hit Discovery, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Cambridge, UK. Electronic address: delyan.ivanov1@astrazeneca.com. |
| Πηγή: | SLAS discovery : advancing life sciences R & D [SLAS Discov] 2026 Aug; Vol. 41, pp. 100308. Date of Electronic Publication: 2026 Apr 04. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: SAGE Publications Country of Publication: United States NLM ID: 101697563 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2472-5560 (Electronic) Linking ISSN: 24725552 NLM ISO Abbreviation: SLAS Discov Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Thousand Oaks, CA : SAGE Publications, [2017]- |
| Ιατρικοί όροι (MeSH): | Fluorescence Resonance Energy Transfer*/methods , Drug Discovery*/methods , High-Throughput Screening Assays*/methods, Fluorescence ; Humans |
| Περίληψη: | Förster resonance energy transfer (FRET) proximity assays are commonly used in hit discovery for investigating protein-protein interactions, protein modification, molecular glues and small analytes like cyclicAMP or GDP. While they are thought to be robust to artefacts, analyzing their output solely using the ratio of acceptor to donor channel fluorescence intensity hides information about interference. We have observed that in untargeted screening campaigns, with true hit rates around 0.1-0.5 %, up to half of the actives based on ratio can be made up of artefacts. Therefore, using the FRET ratio identifies the wrong equity leading to wasted resources and time in follow-up. We propose a simple computational score to prioritize compounds displaying expected spectral behavior without requiring any extra reads or experimental resources. The score penalizes compounds based on their distance from the theoretical spectral path connecting the medians of an untreated (neutral) control and a full-response control. It is easily tuned based on tool compounds and orthogonal assays and can improve confirmation rate in hit follow-up by over 10-fold. (Copyright © 2026 The Authors. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: FRET; Fluorescence polarisation; Hit discovery; Prioritization; Utility score |
| Entry Date(s): | Date Created: 20260406 Date Completed: 20260610 Latest Revision: 20260703 |
| Update Code: | 20260703 |
| DOI: | 10.1016/j.slasd.2026.100308 |
| PMID: | 41942036 |
| Βάση Δεδομένων: | MEDLINE |
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