Related Experiment Video

Updated: Jan 14, 2026

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
10:44

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

13.7K

Unveiling the Potential of a New β-Cyclodextrin-Suxibuzone Conjugate in Proteasome Regulation

Noemi Bognanni1, Stefania Zimbone2, Maria Laura Giuffrida2

  • 1Dipartimento di Scienze Chimiche, Università degli studi di Catania, V.le A.Doria, 6, 95125, Catania, Italy.

Chemmedchem
|October 16, 2025
PubMed

Insights

A novel suxibuzone-beta-cyclodextrin conjugate (SB-CD) effectively enhances proteasome activity. This conjugate reduces protein buildup in cells, showing therapeutic potential for diseases linked to proteasome dysfunction.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • The proteasome is crucial for protein degradation and maintaining cellular homeostasis.
  • Proteasome dysfunction is linked to neurodegenerative diseases and cancer.
  • Suxibuzone is a known anti-inflammatory drug.

Purpose of the Study:

  • To design and evaluate a novel beta-cyclodextrin conjugate of suxibuzone (SB-CD).
  • To investigate the effect of SB-CD on proteasome activity in vitro and in cells.
  • To assess the therapeutic potential of SB-CD for proteasome-related pathologies.

Main Methods:

  • Synthesis and characterization of the SB-CD conjugate.
  • Assay of proteasome activity using purified human 20S core particle.
  • Cellular studies using differentiated human neuroblastoma SH-SY5Y cells (dSHSY5Y).
  • High-resolution electrospray ionization mass spectrometry for cellular uptake and stability studies.

Main Results:

  • SB-CD enhanced the proteolytic activity of the 20S proteasome in a dose-dependent manner.
  • SB-CD demonstrated higher efficacy than suxibuzone alone, with low EC50 values for chymotrypsin-like and trypsin-like activities.
  • SB-CD treatment reduced the accumulation of ubiquitinated proteins in dSHSY5Y cells.
  • Mass spectrometry confirmed SB-CD internalization and stability within cells for up to 24 hours.

Conclusions:

  • The novel SB-CD conjugate is an effective enhancer of proteasome activity.
  • SB-CD shows promise for therapeutic applications in diseases associated with proteasome dysfunction.
  • Further research is warranted to explore the full therapeutic potential of SB-CD.
Keywords:
activatorcyclodextringlycoconjugateproteasomepyrazolone

More Related Videos

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

3.1K
Detection of Protein Ubiquitination Sites by Peptide Enrichment and Mass Spectrometry11:54

Detection of Protein Ubiquitination Sites by Peptide Enrichment and Mass Spectrometry

Published on: March 23, 2020

10.2K

Related Concept Videos

The Proteasome Structure01:17

The Proteasome Structure

The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
1.6K
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.1K
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
1.6K
Regulated Protein Degradation02:58

Regulated Protein Degradation

It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.7K
Drug Metabolism: Phase II Reactions01:14

Drug Metabolism: Phase II Reactions

Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
4.9K