PROTAC’s: Making the “undruggable,” druggable? -Rana Dawood
Stress Fibers and Microtubules in Human Breast Cancer Cells, Unsplash
Let’s delve into the latest therapy taking the scientific world by storm- PROTAC’s. So, what are PROTAC’s and why are they the focus of so many scientific minds? PROTAC stands for PROteolysis TArgeting Chimera, you can think of proteolysis as the body’s own personal protein recycling bin system, and a PROTAC as a hijacker of this system. Proteolysis is the natural breakdown of proteins in the body by these nifty little units called enzymes. A large enzyme family called E3 Ubiquitin ligase enzymes are a common PROTAC target, as they are the main protein degraders in the body. The structure of a PROTAC can be broken into three segments. The 1st binds to the target protein we want to breakdown, the 2nd segment being what binds to the E3 Ubiquitin Ligase enzyme, and the 3rd being the linker between the two to bring them together and- BAM no more protein! Sounds easy enough? Now bring that process and factor in all the complex and intertwining systems of the human body, you can imagine how complicated it can get. In reality, the triangle schematic representation below is the bare-bones visualisation of this therapeutic, imagine a long mass of