How Can A Molecular Glue Degrader Help To Treat Cancer?

A company spun off from The Institute of Cancer Research has developed a molecular glue degrader that has entered a combined Phase I/II clinical trial which it claims could be a breakthrough for cancer drug research and private oncology.

The announcement by Monte Rosa Therapeutics is another step on the long journey for a promising type of cancer treatment that has been theorised for decades but only recently has managed to manifest in the form of promising drug discoveries.

The focus, in this case, is the creation of a type of drug known as a molecular glue degrader, which uses the concept of the molecular glue to stick a protein degradation protein to a target cancer protein, which signposts a multi-protein proteasome to consume both and destroy the cancer cell.

The basic principle was initially explored in the 1990s when researching the potential for the infamous drug thalidomide as a potential treatment for cancer and found that it was an early example of a molecular glue, albeit one that was astonishingly unsafe and unfit for purpose in the 1950s.

They function similarly to another specially designed type of drug known as a proteolysis targeting chimaera (PROTAC). Both use a family of proteins called E3 ligases although whilst molecular glues only have the E3 ligase to create direct interactions, PROTACs consist of three separate components.

They are made up of a binder that connects to a target protein, another connected to an E3 ligase and a linking joint that sticks them together to create the same function and break down a cancerous protein.

This makes them much bigger, which can be a limiting factor when trying to make drugs for certain types of cancers, a problem that molecular glue degraders do not have.

It is very early to say what the effect will be in the long term, as the Phase I/II clinical trial will take some time to complete.