Title:A Mini-Review on Thalidomide: Chemistry, Mechanisms of Action, Therapeutic Potential and Anti-Angiogenic Properties in Multiple Myeloma
Volume: 24
Issue: 25
Author(s): Annalisa Mercurio , Giulia Adriani , Alessia Catalano , Alessia Carocci , Luigia Rao , Giovanni Lentini , Maria M. Cavalluzzi , Carlo Franchini , Angelo Vacca and Filomena Corbo *
Affiliation:
- Department of Pharmacy- Drug Sciences, University of Bari “A. Moro”, Bari,Italy
Keywords:
Thalidomide, angiogenesis, TNF-α, IL-6, VEGF, thalidomide analogs.
Abstract: Thalidomide is a drug with interesting therapeutic properties but also with severe
side effects which require a careful and monitored use. Potential immunomodulatory, antiinflammatory,
anti-angiogenic and sedative properties make thalidomide a good candidate for
the treatment of several diseases such as multiple myeloma. Through an increase in the degradation
of TNFα-mRNA, thalidomide reduces the production of TNFα by monocytes and
macrophages stimulated by lipopolysaccharide or by T lymphocytes induced by mitogenic
stimuli. The decreased level of TNFα alters the mechanisms of intracellular transduction by
preventing the activation of NF-kB and by decreasing the synthesis of proteins, in particular
IL-6, involved in cell proliferation, inflammation, angiogenesis and protection from apoptosis.
Furthermore, thalidomide affects VEGF levels by down-regulating its expression. Nowadays,
new safer and less toxic drugs, analogs of thalidomide, are emerging as beneficial for a more
targeted treatment of multiple myeloma and several other diseases such as Crohn's disease,
rheumatoid arthritis, sarcoidosis, erythema nodosum leprosum, graft-versus-host disease.