Rapamycin acts by first binding to FKBP, forming a complex that then interacts with mTOR.

“From that point of view, it's a very unique kind of drug where it doesn't directly bind to a protein target, but rather it first binds to one target. And now that drug receptor complex has a new surface on it, which now, in this case, interacts with mTOR.”

“yes the complexity around first of all how many of these things there are and how you can change their properties by which ones you're binding to”

“you think about tor being the target of rapamycin it's not exactly the target of rapamycin is an immunofillin called fk binding proteins or fkbp and there's several of these there's three different classes of immunophyllans the complex”

“biochemically rapamycin is a specific inhibitor of mtor complex one so the way rapamycin works is it actually it's a small molecule that binds to another protein called fkbp12 or fpr1 in yeast and once rapamycin binds to fkbp12 that complex of rapamycin with fkbp12 goes to mtor complex one and you can think of it as sort of just messing it up breaks it apart so it inhibits mtor complex one when rapamycin is bind to fkbp12”

“Rapamycin is quite unique and in another aspect that we haven't talked about but also was very exciting at the time right Rapamycin unlike most drugs right most drugs go and find their protein Target and do something usually inhibit that Target Rapamycin gets in the cell binds to a little protein FKBP what it does to FKBP frankly doesn't seem to matter at all but instead hijacks that protein and now takes it and makes it bind to mtor it basically uses it as this thing that it draws next to mtor and that moving of FKBP to mtor is actually critical for how Rapamycin acts and as as people like Stuart shriber have pioneered it's it's really a molecular glue it connects mtor and FK p and that interaction is absolutely critical”

“it's it's really a molecular glue that connects mtor and fkbp and that interaction is absolutely critical”

“rapamycin unlike most drugs right most drugs go and find their protein Target and do something usually inhibit that Target rapy gets in the cell binds to a little protein fkbp what it does to fkbp frankly doesn't seem to matter at all but instead hijacks that protein and now takes it and makes it bind to mtor it basically uses it as this thing that it draws next to mtor and that moving of fkbp to mtor is actually critical for how rapmon acts”