A small-molecule drug inhibits autophagy gene expression through the central regulator TFEB

Significance Autophagy is an orderly degradation mechanism in eukaryotic cells. It is often dysregulated in a range of human diseases, including cancer. Some cancers rely on autophagy to survive and develop. In particular, tumor cells can use autophagy to cope with the cytotoxicity of certain anticancer drugs. Inhibition of autophagy is a promising strategy for tumor therapy. However, there are currently no effective autophagy inhibitors available for clinical use. We show that targeting the central regulatory transcription factor EB (TFEB) can effectively inhibit autophagy at the transcriptional level. And we found that the United States Food and Drug Administration (FDA)-approved drug Eltrombopag is actually a potent autophagy inhibitor targeting TFEB. This finding may help accelerate effective inhibition of autophagy in clinical practice.

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