# The tyrosine kinase inhibitor Gefitinib reduces C. elegans stress-induced sleep, but not likely via LET-23/EGFR inhibition

## TL;DR

Gefitinib, a cancer drug, affects sleep in C. elegans but not by blocking its EGFR-like protein LET-23.

## Contribution

Shows Gefitinib disrupts C. elegans stress-induced sleep without inhibiting LET-23 signaling.

## Key findings

- Gefitinib disrupts stress-induced sleep in C. elegans.
- Gefitinib does not affect EGF overexpression-induced sleep or vulva induction.
- Gefitinib's effect on sleep is likely due to an off-target mechanism.

## Abstract

The anticancer drug
Gefitinib
is a tyrosine kinase inhibitor with selectivity for the Epidermal Growth Factor Receptor (EGFR/ErbB1). As the
C. elegans
EGF receptor
LET-23
shares notable structural homology over its kinase domain with human EGFR, we wished to examine whether
Gefitinib
treatment can interfere with LET-23-dependent processes. We show that
Gefitinib
disrupts
C. elegans
stress-induced sleep (SIS) but does not impact EGF overexpression-induced sleep nor vulva induction. These findings indicate that
Gefitinib
does not interfere with
LET-23
signaling and impairs SIS through an off-target mechanism.