Related Experiment Video

Updated: Jan 28, 2026

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells
09:51

Author Spotlight: A Selective Luciferase-Based Assay for Monitoring ATG4B 27 Activity in Cells

Published on: June 30, 2023

1.4K

Vectorized ULK1/2 and VPS34 Inhibitors for Tissue-Selective Autophagy Inhibition in Oncology

Lorenzo Cianni1, Kathryn Jacobs2,3, Sergei Grintsevich1

  • 1Laboratory of Medicinal Chemistry (UAMC), Department of Pharmaceutical Sciences, University of Antwerp, 2610 Wilrijk, Belgium.

Journal of Medicinal Chemistry
|January 26, 2026
PubMed

Insights

Researchers developed novel tumor-targeted autophagy inhibitors to selectively block cancer cell survival mechanisms. These compounds show promise for cancer therapy by inhibiting autophagy specifically in tumors while sparing healthy tissues.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Autophagy is a key cellular process crucial for survival and homeostasis.
  • Tumors exploit autophagy for plasticity, adaptation, and therapy resistance, making it a therapeutic target.
  • Selective autophagy inhibition in tumors is essential due to its vital role in healthy tissues.

Purpose of the Study:

  • To design and validate tumor-targeted autophagy inhibitors.
  • To develop compounds that selectively inhibit autophagy initiation factors (ULK1/2 and VPS34) in cancer cells.
  • To explore novel therapeutic strategies for oncology.

Main Methods:

  • Design of autophagy initiation factor inhibitors (ULK1/2 and VPS34) with tumor-targeting vectors.
  • Utilized a low-nanomolar ULK1/2 inhibitory scaffold combined with an RGR-sequence targeting peptide.
  • Validated compounds through in vitro, in cellulo, and in vivo preclinical models.

Main Results:

  • Developed promising tumor-targeted autophagy inhibitors.
  • Demonstrated selective activity of the compounds in preclinical models.
  • Showcased preserved efficacy of the inhibitors in targeting tumor-specific autophagy.

Conclusions:

  • The developed compounds are the first examples of tumor-targeted autophagy inhibitors.
  • These inhibitors offer a new approach for tissue-specific modulation of autophagy.
  • Potential applications exist in oncology and other fields requiring autophagy regulation.

More Related Videos

Ferritinophagy: Assessing the Selective Degradation of Iron by Autophagy in Human Fibroblasts09:21

Ferritinophagy: Assessing the Selective Degradation of Iron by Autophagy in Human Fibroblasts

Published on: February 23, 2024

1.5K
Activating Autophagy by Aerobic Exercise in Mice08:44

Activating Autophagy by Aerobic Exercise in Mice

Published on: February 3, 2017

12.7K

Related Concept Videos

Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
5.8K
Feedback Inhibition00:46

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
57.1K
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
91.9K
What is Natural Selection?01:32

What is Natural Selection?

Natural selection is an evolutionary process in which individuals with survival-promoting traits reproduce at higher rates. These favorable traits become more common within a population or species. Naturally selected traits initially arise via random genetic mutations. In order for selection to occur, there must be variation within a population, the trait controlling the variation must be heritable, and there must be an evolutionary advantage for variation in the trait.
128.1K
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
6.0K