Proteolysis-targeting chimera (PROTAC) compounds developed at the University of Dundee are being made available free of charge by the pharmaceutical company Boehringer Ingelheim through their scientific crowdsourcing platform opnMe.com. The opnMe portal provides free and open access to selected molecules for the scientific community aiming at accelerating research initiatives that can benefit patients with high unmet medical need.
PROTACs destroy target proteins rather than just inhibiting them. PROTAC VZ185 was discovered by Vittoria Zoppi, Scott Hughes, Chiara Maniaci and Andrea Testa within the academic group of Professor Alessio Ciulli from the School of Life Sciences at the University of Dundee. The compound potently induces fast and highly selective degradation of the proteins Brd7 and Brd9 inside living cells. It is therefore referred to as a “dual Brd7/Brd9 degrader”.
Professor Ciulli explained, “Brd7 and Brd9 are components of an important multi-protein complex called BAF/PBAF. This complex is often dubbed as the "guardian of the epigenome” because it plays a crucial role in the regulation of gene expression. Processes involving the complex go awry in many diseases, including certain types of cancer, which have been found to depend on the activity of these proteins. If you remove them from the cancer cell, the cancer cell is vulnerable and dies, but not the normal cell.”
Both the active and its inactive parent molecule cis-VZ185 (only binds Brd7/Brd9 without degrading them) will be made available on the platform.
“We hope that by open sharing these compounds, it will allow researchers to perform experiments in ways that would not have been otherwise possible and will help elucidate the roles of Brd7 and Brd9 in normal and disease cell processes. It is therefore expected that sharing the compounds will catalyse and accelerate new discoveries and advances in this exciting new area of science.”
These PROTAC compounds (VZ185 and cis-VZ185) join others that have been previously made available, for example the Dundee-developed BET degrader MZ1, and the joint Dundee-BI’s SMARCA2/4 degrader ACBI1. These compounds are available now, for free to the rest of the world via BI’s opnMe.com open innovation portal.