H. Lee Moffitt Cancer Center and Research Institute Inc.
07/23/2026 | Press release | Distributed by Public on 07/23/2026 13:23
Moffitt Scientists Pioneer Next Generation Covalent Chemistry to Build Safer Precision Medicines
Moffitt Scientists Pioneer Next Generation Covalent Chemistry to Build Safer Precision Medicines
July 23, 2026
Key Highlights
Researchers developed a new chemical building block that helps targeted drugs bind more precisely to cancer-driving proteins while reducing unwanted interactions with healthy proteins.
In laboratory testing, the new approach performed as well as an FDA-approved lung cancer drug while showing greater precision in the proteins it targeted.
In animal studies, the redesigned drug matched the approved therapy's tumor-fighting ability while achieving better drug exposure and showing no obvious signs of toxicity.
Because the new chemistry can be added to existing drug candidates late in development, it could help researchers improve many targeted medicines for cancer and other diseases.
TAMPA, Fla. - Researchers at Moffitt Cancer Center have developed a new chemical approach that could help make targeted cancer medicines safer and more precise. The discovery gives scientists a new way to design drugs that bind more selectively to cancer-driving proteins while reducing unwanted interactions that can lead to side effects.
The findings, published in Science, could help improve a wide range of targeted cancer therapies and eventually medicines for other diseases.
Covalent inhibitors are among the most powerful targeted cancer drugs because they permanently attach to disease-driving proteins, keeping them switched off longer than traditional medicines. More than a dozen covalent drugs have already been approved to treat cancer.
However, the same chemical groups that allow these drugs to bind to cancer proteins can also react with healthy proteins. Those unintended interactions have been linked to side effects and have limited how broadly this type of drug can be used.
To address that challenge, a team led by Justin M. Lopchuk, Ph.D., associate member in Moffitt's Drug Discovery Department, developed a new type of chemical "warhead" built around a small, highly strained molecular structure called a bicyclobutane. The new design strongly prefers binding to cysteine, the amino acid targeted by most approved covalent cancer drugs, while avoiding many of the unwanted reactions seen with existing chemistries.
The researchers also developed a simple way to add the new chemistry to drug candidates late in development. Instead of designing an entirely new drug, scientists can replace the older chemical group on medicines that are already well understood, making it easier to create improved versions of existing therapies.
To test the approach, the team redesigned several experimental and approved cancer drugs, including dacomitinib, an FDA-approved treatment for certain lung cancers. The modified version maintained its ability to block its intended cancer target while interacting with far fewer unintended proteins.
The researchers then tested the redesigned drug in mice with human lung tumors. It reduced tumor growth as effectively as the approved medicine while showing improved drug exposure in the body and no obvious signs of toxicity during the study.
"Covalent drugs are powerful, but their reactivity has always cut both ways," Lopchuk said. "We wanted a warhead that only reacts where it's supposed to. That gave us much cleaner compounds without sacrificing potency."
Researchers warn that additional studies are needed before the technology can be tested in patients. However, because the chemistry can be incorporated into existing drug candidates, they believe it could provide a practical way to improve many targeted medicines without starting the drug discovery process from scratch.
"Because we can install these groups so late in the process, the approach could give drug developers a new, practical way to design safer targeted therapies without giving up the effectiveness patients need," Lopchuk said.
This study was supported by the National Institutes of Health (R35-GM142577, P30-CA076292), the Moffitt Cancer Center Lung Cancer Center of Excellence, a Moffitt Team Science Award and the Moffitt Foundation.
About Moffitt Cancer Center
Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 58 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt's scientific excellence, multidisciplinary research, and robust training and education. Moffitt's expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet status, its highest distinction. For more information, call 1-888-MOFFITT, visit MOFFITT.org, and follow the momentum on Facebook, X, Instagram and YouTube.
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H. Lee Moffitt Cancer Center and Research Institute Inc. published this content on July 23, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on July 23, 2026 at 19:23 UTC. If you believe the information included in the content is inaccurate or outdated and requires editing or removal, please contact us at [email protected]