A sensitive Interactome-based approach to characterize drug activity in living human cells
Abstract
Abnormal protein-protein interactions (PPIs) involving signaling proteins contribute to numerous human diseases. Targeting such aberrant PPIs with selective inhibitory molecules is a promising therapeutic strategy, yet assessing how many PPIs are affected by a candidate drug, and whether inhibition occurs before or after complex assembly, remains technically challenging. Here, we present a live-cell methodology that captures drug-sensitive PPIs by integrating drug-induced cellular responses with interaction mapping. As a proof of concept, we identify extracellular signal-regulated kinase 1 PPIs that are selectively altered by a novel chemical molecule exhibiting antitumor efficacy. We further apply complementary real-time imaging tools to visualize the dissociation of preassembled extracellular signal-regulated kinase 1-cofactor complexes in living cells. Our approach provides a generalizable framework for decoding drug activity on PPIs for virtually any protein target, enabling more precise and physiologically relevant evaluation of therapeutic mechanisms.
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BibTeX
@article{kundlacz2026sensitive,
title = {{A sensitive Interactome-based approach to characterize drug activity in living human cells}},
author = {Cindy Kundlacz and Christelle Forcet and Nawal Hajj Sleiman and Samantha Vonau and Frédéric Marmigère and Benjamin Gillet and Sandrine Hughes and Laurent Gilquin and Hélène Duplus and Agnès Dumont and Gaël Yvert and Françoise Bleicher and Arnaud Gautier and Isabelle Coste and Toufic Renno and Samir Merabet},
journal = {Journal of Biological Chemistry},
year = {2026},
month = sep,
doi = {10.1016/j.jbc.2026.113557},
url = {https://cnrs.hal.science/hal-05772402v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - A sensitive Interactome-based approach to characterize drug activity in living human cells
AU - Cindy Kundlacz
AU - Christelle Forcet
AU - Nawal Hajj Sleiman
AU - Samantha Vonau
AU - Frédéric Marmigère
AU - Benjamin Gillet
AU - Sandrine Hughes
AU - Laurent Gilquin
AU - Hélène Duplus
AU - Agnès Dumont
AU - Gaël Yvert
AU - Françoise Bleicher
AU - Arnaud Gautier
AU - Isabelle Coste
AU - Toufic Renno
AU - Samir Merabet
PY - 2026
DA - 2026/09/17
JO - Journal of Biological Chemistry
DO - 10.1016/j.jbc.2026.113557
UR - https://cnrs.hal.science/hal-05772402v1
AB - Abnormal protein-protein interactions (PPIs) involving signaling proteins contribute to numerous human diseases. Targeting such aberrant PPIs with selective inhibitory molecules is a promising therapeutic strategy, yet assessing how many PPIs are affected by a candidate drug, and whether inhibition occurs before or after complex assembly, remains technically challenging. Here, we present a live-cell methodology that captures drug-sensitive PPIs by integrating drug-induced cellular responses with interaction mapping. As a proof of concept, we identify extracellular signal-regulated kinase 1 PPIs that are selectively altered by a novel chemical molecule exhibiting antitumor efficacy. We further apply complementary real-time imaging tools to visualize the dissociation of preassembled extracellular signal-regulated kinase 1-cofactor complexes in living cells. Our approach provides a generalizable framework for decoding drug activity on PPIs for virtually any protein target, enabling more precise and physiologically relevant evaluation of therapeutic mechanisms.
SN - 0021-9258
SN - 1083-351X
ER -