Related Experiment Video

Updated: May 21, 2026

A Fluorescence-based Protocol for Preliminary Screening of Protein Synthesis Inhibitors from Natural Sources
10:24

A Fluorescence-based Protocol for Preliminary Screening of Protein Synthesis Inhibitors from Natural Sources

Published on: January 27, 2026

Targeting the proteasome in cancer therapy: development and future opportunities in natural products

Xiu Zhao1, Shanshan Liu1, Xinrui Zeng1

  • 1Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug, West China School of Pharmacy, Sichuan University, Chengdu, China.

Frontiers in Pharmacology
|May 20, 2026
PubMed
Abstract

Insights

Natural products offer new hope for overcoming resistance to proteasome inhibitors (PIs) in multiple myeloma. Exploring these compounds can lead to next-generation therapies to improve patient outcomes.

Area of Science:

  • Oncology
  • Pharmacology
  • Drug Discovery

Background:

  • The ubiquitin-proteasome pathway is a key therapeutic target in multiple myeloma.
  • Proteasome inhibitors (PIs) are a cornerstone of multiple myeloma treatment.
  • Resistance to PIs necessitates the development of novel therapeutic strategies.

Purpose of the Study:

  • To review the clinical applications of PIs in multiple myeloma.
  • To summarize natural products targeting the proteasome or enhancing PI sensitivity.
  • To discuss the potential of natural product-derived PIs in overcoming resistance.

Main Methods:

  • Literature review of clinical trials and studies up to 2025.
  • Databases searched include PubMed, Web of Science, Google Scholar, and ClinicalTrials.gov.
  • Focus on biological activities, structure-activity relationships, and clinical outcomes.

Main Results:

  • Current clinical applications of PIs are summarized.
  • Natural products directly targeting the proteasome or enhancing PI sensitivity are highlighted.
  • The clinical progress of marizomib, a natural product-derived PI, is discussed.

Conclusions:

  • Natural product-derived PIs show significant potential for next-generation therapies.
  • Combination strategies with natural products may overcome cancer resistance.
  • The structural diversity of natural products supports continued drug discovery efforts.
Keywords:
cancer therapydrug resistancemultiple myelomanatural productproteasome inhibitor

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

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
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 (ubiquitin...
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...
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...
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...