March 27, 2025
The top three most ordered molecules on opnMe in 2024 have one thing in common. They all emerged from a research collaboration between the Centre of Targeted Protein Degradation (CeTPD) at the University of Dundee and Boehringer Ingelheim.
Specifically, they belong to a novel class of molecules known as proteolysis targeting chimeras (PROTACs) which can be employed to degrade cellular proteins in a targeted manner by exploiting the endogenous cellular ubiquitin-proteasome system.
The list is topped by the degrader ACBI3 that targets a broad spectrum of KRAS variants which collectively belong to one of the most mutated oncogenes in human cancers. The two runner-ups, ACBI1 and ACBI2, target the SMARCA2 subunit of the chromatin remodeling complex BAF and can therefore be exploited to study epigenetic mechanisms associated with disease. ACBI2 stands out as it represents one of the first VHL-based PROTAC degraders which is suitable for oral administration in preclinical disease models.
Together, the three molecules have been shared with more than 100 laboratories in 22 countries via Boehringer’s open innovation portal opnMe.com in 2024.
“By making these molecules easily accessible and available free of charge via opnMe, we hope to stir several new research directions that may increase our insights in fundamental cellular mechanisms affecting both basic science and our understanding and targeting of disease biology.”, says Alessio Ciulli, Director of CeTPD.
“It´s exciting to partner with brilliant teams to explore novel therapeutic avenues for patients. The Centre of Targeted Protein Degradation emerged as a center of excellence for removing disease causing proteins, and Boehringer is proud to have established this partnership almost ten years ago”, adds Peter Ettmayer, Head of Drug Discovery Sciences Vienna, Boehringer Ingelheim.
“The significant contribution of the three targeted degraders to the success of the opnMe portal shows how avidly novel drug targeting concepts are picked up by scientific community” says Florian Montel, Head of OpenScience at Boehringer Ingelheim. “We are extremely satisfied to see how our open innovation portal can contribute to the acceleration of novel scientific discoveries and we are proud to make these well-characterized molecules available to scientists across the world”, he adds.
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About the 2024 top 3 molecules
All three PROTAC degraders emerged from a collaboration between Professor Alessio Ciulli’s team at the Centre of Targeted Protein Degradation (CeTPD) at the University of Dundee and Boehringer Ingelheim and belong to the von Hippel-Lindau (VHL)-recruiting class. ACBI3 is a first in class PROTAC molecule, potently degrading multiple KRAS variants in vitro and in vivo. Proteolytic degradation of KRAS via ACBI3 enables a greater than 10-fold higher potency compared to target inhibition and results in prolonged suppression of MAPK signaling. ACBI1 is a potent and cooperative PROTAC degrader of the BAF complex subunits SMARCA2, SMARCA4 and PRBM1. It is suitable for both in vitro and in vivo studies and may be a useful tool to study the effects of an acute inactivation of the BAF complex. ACBI2 is a highly potent and orally bioavailable SMARCA2 PROTAC degrader. It shows selective degradation of SMARCA2 over SMARCA4 in ex vivo human whole blood assays.
About opnMe
opnMe.com, the open innovation portal of Boehringer Ingelheim, fosters science and collaboration initiatives in areas of high unmet medical need. As part of our first pillar, the “Molecules to Order”, we share well-characterized tool compounds free of charge with no IP strings attached. These are complemented by “Molecules for Collaboration” where we offer access to unprecedented, often unpublished molecules, together with an attractive funding package. Interested scientists are invited to submit testable research hypotheses with these assets in novel diseases or combinations. With our “opn2EXPERTS” program, we enlist scientific advice on key biologic issues to fuel further drug discovery and deliver novel solutions that benefit unmet patient needs. Our opn2TALENTS PostDoc grants provide an opportunity for high-caliber talents to pitch their scientific approaches for well-defined research questions to conduct their research at one of our discovery research sites.