Unlocking the Undruggable: EUbOPEN-Funded Research Achieves Breakthrough in Targeting SOCS Proteins for Disease Treatment

A team in the laboratory of Professor Alessio Ciulli, at the Dundee University’s Centre for Targeted Protein Degradation (CeTPD), has unlocked a class of proteins known as suppressor of cytokine signalling (SOCS). SOCS proteins contain a crucial structural portion called the SH2 domain which, until now, was thought of being undruggable.
The SOCS2 protein is involved in many diseases, including cancer and inflammatory diseases, but until now, no small molecule has been generated that successfully inhibits the protein.
One of the major research interests of the Ciulli Lab is the targeting of E3 ligase complexes, and SOCS2 is part of one such complexes. These complexes initiate the recycling of proteins in the cell, by earmarking abnormal proteins for destruction.
It is possible to induce this process using carefully designed molecules, known as PROTACs, however this requires molecules that tightly bind E3 ligases - SOCS2 is an example of one such ligase. The research team has designed a molecule that does exactly that, offering a chemical tool able to study the function of these proteins and manipulate them in ways not previously possible.
The research, funded by the European Research Council (ERC) and the Innovative Medicine Initiative 2 consortium EUbOPEN, is published in the journal Nature Communications. Read the full press release here.

The EUbOPEN (Enable and Unlock biology in the OPEN) consortium  is a public-private partnership, which aims to develop high quality chemical tool compounds for one third of the druggable proteome. EUbOPEN enables unencumbered access to these research tools, thereby empowering academia and industry alike to explore disease biology and unlock the discovery of new drug targets and treatments.