The Small Molecules Targeting Ubiquitin-Proteasome System for Cancer Therapy

Comb Chem High Throughput Screen. 2017;20(5):403-413. doi: 10.2174/1386207320666170710124746.


Background & aim: The ubiquitin-proteasome system (UPS) is the major pathway for degrading the intracellular proteins. The 2004 Nobel Prize in Chemistry was awarded to Rose, Hershko, and Ciechanover to highlight the fundamental importance of UPS.

Method & results: The alterations in this process have been shown to contribute to the cancer progression. Hence, UPS has become a popular target for developing chemotherapeutics against tumours. The application of bortezomib showed high efficiency in treating haematological malignancies by interfering with UPS activity. Many compounds are being screened and evaluated in recent pharmacological advances, either as single agents or in synergy with other drugs, and more to be revealed.

Conclusion: In the present review, we exhibit the crucial ingredients involved in UPS and discuss the current situation of small molecules targeting various components of ubiquitination pathway in cancer treatment.

Keywords: E3 ligase; Ubiquitin; cancer; deubiquitinating enzyme; proteasome; small molecule inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Bortezomib / pharmacology
  • High-Throughput Screening Assays
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Proteasome Endopeptidase Complex / metabolism*
  • Proteasome Inhibitors / chemistry
  • Proteasome Inhibitors / pharmacology*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology*
  • Ubiquitin / antagonists & inhibitors*
  • Ubiquitin / metabolism


  • Proteasome Inhibitors
  • Small Molecule Libraries
  • Ubiquitin
  • Bortezomib
  • Proteasome Endopeptidase Complex