Single molecule tracking based drug screening

Watanabe, Daisuke; Hiroshima, Michio; Yasui, Masato et al.

Nature Communications, 2024, 15, 8975

Number of Access:522（2025-07-26 11:58 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98552

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Title
Single molecule tracking based drug screening
Creator
CreatorName
Watanabe, Daisuke
NRID
1000020392087 1000020392087
researchmap permalink
read0208996 read0208996
CreatorName
Hiroshima, Michio
CreatorName
Yasui, Masato
NRID
1000040444517 1000040444517
ORCID
0000-0002-9354-3404 0000-0002-9354-3404
researchmap permalink
MasahiroUeda2018-SBC MasahiroUeda2018-SBC
Scopus Author ID
35303650000 35303650000
CreatorName
Ueda, Masahiro
Description
Watanabe D., Hiroshima M., Yasui M., et al. Single molecule tracking based drug screening. Nature Communications 15, 8975 (2024); https://doi.org/https://doi.org/10.1038/s41467-024-53432-w.
Abstract
The single-molecule tracking of transmembrane receptors in living cells has provided significant insights into signaling mechanisms, such as mobility and clustering upon their activation/inactivation, making it a potential screening method for drug discovery. Here we show that single-molecule tracking-based screening can be used to explore compounds both detectable and undetectable by conventional methods for disease-related receptors. Using an automated system for a fast large-scale single-molecule analysis, we screen for epidermal growth factor receptor (EGFR) from 1134 of FDA approved drugs. The 18 hit compounds include all EGFR-targeted tyrosine kinase inhibitors (TKIs) in the library that suppress any phosphorylation-dependent mobility shift of EGFR, proving the concept of this approach. The remaining hit compounds are not reported as EGFR-targeted drugs and do not inhibit EGF-induced EGFR phosphorylation. These non-TKI compounds affect the mobility and/or clustering of EGFR without EGF and induce EGFR internalization, to impede EGFR-dependent cell growth. Thus, single-molecule tracking provides an alternative modality for discovering therapeutics on various receptor functions with previously untargeted mechanisms.
Publisher
Nature Research
Source Title
Nature Communications
Volume (Issue)
15
Page
8975
Date of Issued
2024-10-17
Language
English
Handle URL
https://hdl.handle.net/11094/98552
eISSN
20411723
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1038/s41467-024-53432-w
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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Category
学術雑誌論文 Journal Article