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Updated: Jul 16, 2026
10:44
Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
The thalidomide saga
1Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA. Melcheme@moffitt.usf.edu
The International Journal of Biochemistry & Cell Biology
|March 21, 2007
Summary
Thalidomide and its analogs are immunomodulatory drugs (IMiDs) that treat cancer and inflammatory diseases by suppressing cytokines and angiogenesis. These drugs, including lenalidomide, show promise in various conditions.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- Thalidomide, initially a sedative, is now recognized as an immunomodulatory drug (IMiD).
- It exhibits anti-inflammatory and anti-angiogenic properties by modulating cytokine production and signaling pathways.
- Its analogs, lenalidomide and CC-4047, offer enhanced potency and therapeutic potential.
Purpose of the Study:
- To review the pharmacokinetic and biologic effects of thalidomide and its analogs.
- To explore their mechanisms of action in malignant and inflammatory conditions.
- To discuss their therapeutic applications and ongoing investigations.
Main Methods:
- Literature review of studies on thalidomide and its analogs.
- Analysis of biological effects, including cytokine modulation, T-cell activation, and angiogenesis inhibition.
- Examination of pharmacokinetic profiles and clinical applications.
Main Results:
- Thalidomide suppresses tumor necrosis factor-alpha (TNF-alpha) and pro-inflammatory cytokines.
- It inhibits vascular endothelial growth factor (VEGF) and beta fibroblast growth factor (bFGF), antagonizing neoangiogenesis.
- Lenalidomide and CC-4047 demonstrate enhanced potency in these effects and are approved for multiple myeloma and myelodysplastic syndromes.
Conclusions:
- Thalidomide and its analogs are effective immunomodulatory drugs with broad therapeutic applications.
- Their mechanisms involve cytokine suppression, T-cell activation, and anti-angiogenesis.
- Ongoing research continues to explore their potential in various cancers and inflammatory diseases.
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