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Inhibitors of the ATPase p97/VCP: From basic research to clinical applications

Susan Kilgas1, Kristijan Ramadan1

  • 1Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.

Cell Chemical Biology
|January 14, 2023
PubMed

Insights

Protein degradation pathways, including the ubiquitin-proteasome system (UPS) and autophagy, are crucial for cellular health. Inhibitors targeting the ATPase p97 (VCP) show promise as cancer therapies by disrupting these pathways.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Biochemistry

Background:

  • Protein homeostasis is vital, with deficiencies linked to cancer and neurodegenerative diseases.
  • The ubiquitin-proteasome system (UPS) and autophagy are key protein degradation pathways.
  • The ATPase p97 (VCP) is a central regulator of both UPS and autophagy.

Purpose of the Study:

  • To review the development of p97 inhibitors.
  • To highlight their evolution as research tools and therapeutic agents.
  • To discuss their potential in cancer therapy.

Main Methods:

  • Review of existing literature on p97 inhibitors.
  • Analysis of clinical trial data for compounds like CB-5083 and CB-5339.
  • Examination of p97's role in protein degradation and autophagy.

Main Results:

  • p97 inhibitors, such as CB-5083 and CB-5339, have demonstrated significant anti-tumor activity.
  • These inhibitors are progressing through clinical trials.
  • p97 inhibition offers a novel strategy for targeting protein degradation in cancer.

Conclusions:

  • p97 inhibitors represent a promising therapeutic avenue for cancer.
  • Their development signifies progress in targeting protein degradation pathways.
  • Further research into p97 inhibitors could yield effective treatments for various diseases.
Keywords:
CB-5083CB-5339anti-inflammatoryantimicrobialcancer therapyp97 inhibitorsp97/VCP

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