2015 Antineoplastics

Proteosome inhibitors: BORTEZOMIB, CARFILZOMIB

Mechanism

  • Upiquinization and 26S Proteasome

    http://www.mdpi.com

    inhibitors of the 26S proteosome (a large protein complex that degrades ubiquitinated --- especially misfolded --- proteins)

    • BORTEZOMIB is reversible; CARFILZOMIB is irreversible

  • the ubiquitin-26S proteasome pathway regulates the intracellular concentration of proteins, thereby maintaining cellular homeostasis
    • inhibition of the 26S proteasome affects multiple signalling cascades, triggering apoptosis and leading to cell death

  • the nature of the specific signalling cascades that are affected may confer specificity of these drugsfor cancer vs. normal cells, and determine its effectiveness in one type of cancer vs. another (multiple myeloma cells appear to be particularly susceptible)
Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 11-apr-15 9:39 AM