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Updated: Oct 12, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Published on: May 15, 2019

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Targeting of the FOXM1 Oncoprotein by E3 Ligase-Assisted Degradation

Guoshun Luo1, Xin Lin1, Antonio Vega-Medina2

  • 1State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, P. R. China.

Journal of Medicinal Chemistry
|November 23, 2021
PubMed

Insights

Researchers designed a novel molecule to degrade the FOXM1 oncoprotein, a key target in cancer. This protein-targeting chimera approach shows promise for treating triple-negative breast cancer (TNBC).

Area of Science:

  • Molecular Oncology
  • Drug Discovery

Background:

  • The transcription factor FOXM1 is a crucial regulator of proliferation-related genes and an attractive target in oncology.
  • Current small-molecule inhibitors targeting FOXM1 often suffer from insufficient specificity and efficacy.

Purpose of the Study:

  • To design an effective CRBN-recruiting molecule for targeted FOXM1 protein degradation.
  • To evaluate the in vivo antitumor activity of the designed molecule against triple-negative breast cancer (TNBC) xenografts.

Main Methods:

  • Utilized in silico modeling of the FOXM1 DNA-binding domain (FOXM1-DBD) with inhibitors.
  • Developed a novel protein-targeting chimera strategy to induce FOXM1 protein degradation.

Main Results:

  • Successfully designed a CRBN-recruiting molecule that effectively degrades FOXM1 protein.
  • Demonstrated promising in vivo antitumor activity in TNBC xenograft models.

Conclusions:

  • This study pioneers the use of protein-targeting chimeras to degrade the challenging FOXM1 oncoprotein.
  • Presents a novel therapeutic strategy to counteract the oncogenic role of FOXM1 in cancer.

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