Novartis is seeking to broadly expand the repertoire of human proteins its chemists can drug, and it is partnering with the University of California, Berkeley, to do it.
The Novartis-Berkeley Center for Proteomics & Chemistry Technologies launched today to discover hot spots for forming covalent bonds on the surfaces of otherwise undruggable proteins—those without a clear binding pocket for a drug. Although sometimes these covalent modifications alone can disrupt the protein, the center’s chemists will also design dual-function drugs: At one end they bind a disease-causing protein; at the other end they recruit cellular machinery that tags and ships the protein off to the proteasome, the cell’s garbage disposal.
The alliance’s funding amount is unspecified. Its science is squarely in the wheelhouse of Jay Bradner, president of Novartis Institutes for BioMedical Research (NIBR). Before joining Novartis, Bradner was a cofounder of C4 Therapeutics, a start-up that is also developing targeted protein degradation therapeutics.
The existing labs of Berkeley chemists Chris Chang, Tom Maimone, Daniel Nomura, and Dean Toste will house the new center. “This is a special collaborative effort,” center director Nomura says. “Novartis is sharing chemical resources that we don’t have.”
A recent paper demonstrated the potential of Nomura’s chemoproteomics approach to drug discovery, says John Tallarico, NIBR’s head of chemical biology and therapeutics. Nomura’s team discovered a compound that binds to a colorectal cancer-linked protein called RTN4, which is generally considered undruggable due to its association with the cell’s internal endoplasmic reticulum membranes (Chem. Commun. 2017, DOI: 10.1039/c7cc01480e).
“Normally I would say, ‘That doesn’t look possible,’ ” Tallarico says. “It was quite striking how rapidly they discovered it. This is exactly what we’d like to be able to do on a regular basis.”
Nomura says Berkeley has been supportive of the industry-academia partnership. It helps that Bradner is an outspoken advocate for sharing scientific discoveries.
“There are a lot of Berkeley students involved,” Tallarico says. And although some of the work will be applied to Novartis projects and presumably not be shared, “We also intend to publish work that gets done,” he adds.