When Ray Deshaies joined Amgen in 2017, he brought with him a pioneering spirit and a track record of fundamental discoveries in molecular biology. Now, as Amgen’s Distinguished Science Fellow and former head of Research, Deshaies is emblematic of the caliber of scientists who choose to make their mark at Amgen.
Deshaies and Craig Crews, the John C. Malone Professor of Molecular, Cellular, and Developmental Biology at Yale University recently received the Passano Award, established in 1946. The award celebrates transformative contributions to medical science. More than 20 recipients have gone on to win the Nobel Prize. In naming Deshaies a co-recipient this year, the foundation recognized his groundbreaking work in the development of proteolysis-targeting chimeras (PROTACS), a class of therapeutics that may redefine what’s druggable in human disease.
Studying Cellular Quality Control
Deshaies' journey began with a simple question: How do cells decide when to divide? That question led him to study the ubiquitin-proteasome system, the cell’s built-in quality control and regulatory machinery for protein degradation. His lab's deep dive into this system laid the biochemical foundation for an entirely new way to design drugs — not to inhibit disease-causing proteins, but to eliminate them altogether.
This concept matured into PROTACs, molecules that act as molecular matchmakers, tethering disease-causing proteins to the cell’s degradation machinery.
Similar to PROTACs are molecular “glues,” small molecules that harness the body's biological machinery and inhibit or remove harmful proteins to drive therapeutic effects. One Amgen clinical candidate glue is AMG 193, an investigational small molecule inhibitor of PRMT5 (protein arginine methyltransferase 5), a molecule that helps cancer cells survive. AMG 193 is designed to work by gluing PRMT5 to a molecule called MTA (methylthioadenosine) that builds up in some cancer cells. This may inhibit the function of PRMT5, with the goal of leading to those tumor cells' death.
A PROTAC molecule (at top, middle) is like a piece of double-sided tape that sticks to both a ubiquitin ligase (at left, in green) and a target protein (in dark purple), joining them together. Ubiquitin (in yellow) adds a chain of ubiquitin molecules to tag the target so it is recognized by the proteasome (at right, in light purple), which then degrades the target protein into small peptides. Click image to enlarge.
Building Amgen’s Induced Proximity Platform
At Amgen, Deshaies championed and helped establish the Induced Proximity Platform (IPP), which extends the PROTAC concept even further. Led today by Ryan Potts, vice president of Research, the IPP aims to drug the undruggable — the 85% of proteins that conventional drugs can’t touch — by inducing proximity between targets and cellular systems that can silence, degrade or modulate them.
“Ray’s work embodies the spirit of scientific innovation that drives us at Amgen,” said Potts. “The IPP is one of our most ambitious and promising platforms, and it stands on the foundation Ray helped build.”
A Culture Where Breakthroughs Begin
Deshaies’ journey reflects Amgen’s scientific culture — one that attracts visionary thinkers and gives them room to pursue ideas with the power to transform medicine. While Deshaies was working on the PROTAC concept before joining the company, his leadership helped translate that science into a platform approach that is now core to Amgen’s future in multispecifics.
“Science often advances because of basic curiosity,” Deshaies said during his Passano award lecture. “We weren’t trying to invent a drug — we were trying to understand how nature works. But if you ask the right questions and follow the data, sometimes the result is something that can help people.”
Deshaies’ work — and the team now building on it — shows that when great scientists come to Amgen, they don’t just find a place to work. They find a place to lead.
