BOSTON and SOUTH SAN FRANCISCO, Calif., Jan. 05, 2026 (GLOBE NEWSWIRE) -- Frontier Medicines Corporation, a clinical-stage precision medicines company unlocking the proteome to develop small molecule oncology and immunology drugs against previously undruggable disease-causing targets, today announced the publication of a technological advancement in Nature Communications describing a new diagonal dose-response time-course (dDRTC) method that dramatically accelerates how researchers quantify the efficiency of covalent drug binding, a long-standing bottleneck in covalent hit-to-lead programs. The publication, entitled “A practical method for determining the rate of covalent modification of fragments and leads,” details how the company’s dDRTC method reduces the experimental burden by almost an order of magnitude, enabling accurate kinetic insight earlier, and accelerating structure-activity relationship (SAR) interpretation for lead discovery.
“The dDRTC method we have described in this publication is a significant improvement over traditional DRTC methods, making this approach faster, more scalable, and more practical for SAR. It enables us to reduce the time it takes to understand how well and how rapidly a covalent bond forms,” said Robert Everley, PhD, Senior Director of Chemical Biology at Frontier Medicines. “We have been using dDRTC in-house for more than two years now. Given our pursuit of undruggable targets and our aggressive goal of producing one new drug candidate per year, the dDRTC method has become a critical part of our industry-leading covalent discovery platform. It has helped fuel our growing pipeline.”
Publication Summary:
The most critical parameter for evaluating covalent binding to a protein target is the rate constant kinact/KI. However, existing methods for measuring kinact/KI are time and resource-intensive and involve complex data interpretation. In the paper, Frontier describes the diagonal dose-response time-course (dDRTC), an efficient mass spectrometry-based method for determining kinact/KI, enabling routine quantification of kinact/KI earlier in program development and accelerating SAR interpretation for lead discovery. Frontier validated the approach on a dozen covalent fragments and lead-like modifiers across three biologically and structurally distinct targets, including KRASG12C and two E3 ligase complexes. Results showed a strong correlation with values obtained from the gold-standard full DRTC experiment, demonstrating that dDRTC can reliably quantify kinact/KI over more than three orders of magnitude of potency while significantly sparing resources.
Notably, the paper also includes simulation studies outlining when dDRTC is most effective, positioning it as a practical tool for early hit-to-lead optimization and fragment evolution, in contexts where covalent chemistry is increasingly used but kinetic measurements have historically been inaccessible at scale.
About Frontier Medicines
Frontier Medicines is a clinical-stage precision medicine company pioneering groundbreaking medicines to transform treatment for genetically defined patient populations, starting with oncology and immunology. Our proprietary chemoproteomics-powered drug discovery engine, the Frontier™ Platform, leverages covalent chemistry and machine learning to unlock difficult-to-drug, disease-causing proteins for drug development. Today, we are advancing a diversified pipeline of wholly owned precision medicines against the most critical drivers of cancer and high-value immunology programs. For more information, please visit www.frontiermeds.com. Follow Frontier on LinkedIn.
Media Contact
pr@frontiermeds.com
