Related Experiment Video

Updated: Jun 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

BSc2118 is a novel proteasome inhibitor with activity against multiple myeloma

Jan Sterz1, Christian Jakob, Ulrike Kuckelkorn

  • 1Department of Hematology and Oncology, Charité Universitätsmedizin Berlin, Berlin, Germany. sezer@charite.de; o.sezer@uke.de

European Journal of Haematology
|April 9, 2010
PubMed
Abstract

Insights

The novel proteasome inhibitor BSc2118 demonstrates significant antimyeloma activity by inducing apoptosis and cell cycle arrest in multiple myeloma cells. This agent shows promise for cancer drug development with low toxicity to normal cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • The ubiquitin-proteasome system is a validated therapeutic target in cancer treatment.
  • Multiple myeloma (MM) is a hematological malignancy characterized by uncontrolled proliferation of plasma cells.

Purpose of the Study:

  • To investigate the effects of the novel proteasome inhibitor BSc2118.
  • To evaluate BSc2118's efficacy in both t(4;14) positive and negative multiple myeloma (MM) cells.
  • To assess the safety profile of BSc2118 in normal peripheral blood mononuclear cells (PBMNC).

Main Methods:

  • Exposure of MM cell lines (OPM-2, RPMI-8226, U266) and primary MM cells to BSc2118.
  • Cytotoxicity assessment using MTT assay and apoptosis analysis via annexin-V assay.
  • Evaluation of proteasomal activity, cell cycle progression, and specific molecular markers (p21, NF-kappaB).

Main Results:

  • Bsc2118 exhibited dose-dependent growth inhibition and induced apoptosis in MM cells, irrespective of t(4;14) status.
  • A significant G2-M cell cycle arrest was observed, alongside marked inhibition of proteasome activity and NF-kappaB activation.
  • Low toxicity was noted in normal PBMNC, indicating a favorable therapeutic window.

Conclusions:

  • Bsc2118 demonstrates potent anti-myeloma activity.
  • The novel proteasome inhibitor shows potential as a therapeutic agent in cancer drug development.
  • Further investigation into BSc2118 for multiple myeloma treatment is warranted.

More Related Videos

Utilization of the Soft Agar Colony Formation Assay to Identify Inhibitors of Tumorigenicity in Breast Cancer Cells11:06

Utilization of the Soft Agar Colony Formation Assay to Identify Inhibitors of Tumorigenicity in Breast Cancer Cells

Published on: May 20, 2015

Related Concept Videos

Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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 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...