Illustration of DUBTAC in action against a target. (Courtesy Nomura Lab)
- Novartis-Berkeley Translational Chemical Biology Institute combines Novartis expertise in chemical biology and medicinal chemistry with Berkeley’s expertise in covalent chemoproteomics and chemistry methodologies
- Research collaboration aims to unlock intractable drug targets, discover new therapeutic modalities, and accelerate discovery of new medicines in human diseases
- Successes thus far from the research collaboration include discovery of novel targeted protein degradation strategies, development of a new therapeutic modality for targeted protein stabilization, and a spin-out company
Novartis and the University of California, Berkeley have extended their research-based collaboration to develop new technologies for the discovery of next-generation therapeutics, following its successes over the last five years. The combined research team is pursuing a vast number of disease targets in cancer and other illnesses that have eluded traditional small-molecule compounds and drug discovery strategies.
“One of the biggest challenges facing drug discovery is that the majority of proteins are currently still considered ‘undruggable,’” said covalent chemoproteomics expert Daniel Nomura, Director of the Institute and Professor of Chemistry, Molecular and Cell Biology in the Molecular Therapeutics Division, and Nutritional Sciences and Toxicology at UC Berkeley. “Most proteins do not possess well-defined binding pockets or ‘ligandable hotspots’ that can be pharmacologically and functionally targeted for therapeutic benefit. Tackling these undruggable proteins requires the development of innovative technologies for ligand discovery and the discovery of novel therapeutic modalities to functionally manipulate these intractable proteins for therapeutic benefit.”
The continued research collaboration allows UC Berkeley scientists to work with their scientific peers at Novartis Institutes for BioMedical Research (NIBR) to find new cures for debilitating illnesses. The second phase of the research collaboration is the Novartis-Berkeley Translational Chemical Biology Institute, and is based at UC Berkeley. The Berkeley team includes Professors Nomura, F. Dean Toste, Thomas Maimone, Ziyang Zhang, and James Olzmann. The science and strategy underpinning the research collaboration aim to harness covalency, coupled with chemoproteomics technology, to enable the discovery of small-molecule compounds that could ultimately form the basis of proximity-based therapeutics.
“I am thrilled to be able to help build off the momentum gained during the past five years and equally excited to synergize with new colleagues,” said Maimone, Associate Professor of Chemistry at UC Berkeley. “With expanded scientific expertise, increasingly sophisticated chemistries, and new envisioned therapeutic modalities, the next several years will be exhilarating.”
The inaugural research collaboration, the Novartis-Berkeley Center for Chemistry and Proteomics Technologies, led to multiple groundbreaking discoveries, including the development of several novel recruiters of E3 ubiquitin ligases that can be exploited in the degradation of disease causing proteins; the development of new chemistry that can be used to enhance the scope of covalent chemoproteomic technologies; and the creation of a new therapeutic platform called Deubiquitinase Targeting Chimeras (DUBTACs) for stabilizing the levels of proteins that are aberrantly degraded. This work has led to several publications and patents and facilitated the training of emerging scientists. The DUBTAC platform is also the basis of a spinout company, Vicinitas Therapeutics, focused on developing DUBTACs into a unique, potential, proximity-based therapeutic modality for cancer, genetic disorders, and other indications.
"We joined forces with Berkeley five years ago because we knew that many compelling targets in disease biology remain beyond reach – and that no one team or discipline could tackle the toughest among them alone,” said Jay Bradner, President of NIBR. “Today, we recommit to working shoulder-to-shoulder to make these so-called ‘undruggable’ targets druggable.”
Moving forward, the alliance will continue to develop new chemistries and chemical technologies for targeting undruggable proteins, expand upon emerging therapeutic modalities such as targeted protein degradation (TPD) that exploit the cell’s natural protein disposal system to destroy disease-causing proteins, and develop new therapeutic modalities that enable access into larger swaths of the undruggable protein landscape.
Contact for more information about this research program: email: dnomura@berkeley.edu
Novartis-Berkeley Translational Chemical Biology Institute in the News