What is Cereblon and how is it related to IMiDs?

[Music] what is Sara blonde and how is it related to image it's actually a relatively recent discovery that these drugs as a class tend to function by affecting how this protein Sara blonde works Sara blonde is part of the normal processes of inside the cell of protein degradation typically your body's cells tagged proteins that for degradation and this is a process by which self renewal within the cell during its lifespan occurs the immunomodulatory drugs bind to Sara blonde and lead to targeting of specific proteins called transcription factors for degradation the kuro-san de ellos this family of transcription factors and that has a variety of as I discussed earlier pleiotropic effect seeing my myeloma cells and also in immune cells that are distinct in the sense that it's toxic to myeloma cells and enhances in some ways the activity of some immune cells but the protein itself is intracellular and isn't something that's typically tested on the cell surface Sara bran is is an intracellular molecule that is the target for for all the Iman military agents the lead amide lenalidomide formerly the might and now a red light interesting enough this was not discovered until many years after we have started using those agents and and essentially the Sarah Braun essentially modulates the activity of a to other gene regulators one of them being Icarus and there has been some good attempt of correlate the level of cerebral activity at the level cerebral myeloma cell with activity of those agents although this has not you pinout as of being a true biomarker that can be used for treatment decisions so it's we still know very little about them we know a little bit more than quite a bit more that we knew ten years ago of how those drugs work but we have still very little knowledge of how the resistant develops whether the cerebral expression can or should be used as a biomarker for selection of patients who are best candidates for image in part of that is because it needs have been a widespread success that seems to be a kind of fixture of just about any or the vast majority of myeloma regiments so it kind of has been challenged to find a subset of patients that would not benefit from the human ability reagent so the race has really been about making more specific less toxic more active immunomodulatory agents [Music]