What are proteasome inhibitors?

[Music] what our proteasome inhibitors the proteasome inhibitors essentially target the proteasome and the proteasome has several components to it it's the proteasome is the machinery that the body uses to recycle its proteins to make other proteins and so one can imagine that if you have too much milk in your refrigerator that if you could make that milk into eggs then you would break down the milk and turn it into eggs and so your cells do that all the time with their proteins by using this proteasome myeloma cells are so geared towards making this monoclonal protein that in the absence of a protozoan they really are unable to survive several drugs are available to target the proteasome bortezomib was the first or Velcade was the first one that was developed and it's a reversible binder of the proteasome effective on its own as well as in combination with steroids and other chemo therapeutic drugs and immunomodulatory drugs can its main downside is neuropathy which in many cases is not fully reversible but does improve over time I think about half the patient's we treat develop some modicum of neuropathy carpoza mabh is a newer generation proteasome inhibitor it's an irreversible inhibitor it's effective in individuals who have received prior bortezomib and even who are resistant to bortezomib carfilzomib is administered as an intravenous drug on two consecutive days bortezomib is typically administered as a subcutaneous injection so all of these require visits to the clinic which some of our patients may be a challenge so oral proteasome inhibitors are advantageous from a patient convenience perspective excessive is an oral proteasome inhibitor in the or Testament family and has efficacy as well both alone with steroids or in combination with immunomodulatory drugs [Music]