Mech-Seq™ Technology Enables Industrial-Scale Screening of Drug Candidates by Measuring Functional Efficacy Beyond Binding
Key Insights
Startup company 4ces (search) has developed Mech-Seq™ (search), a technology that analyzes up to 10,000 molecules per hour to determine whether drug candidates actually work, not just bind to their targets.
The platform measures how proteins interact with DNA while tracking structural changes, enabling real-time observation of drug effects on protein function.
Applications span cancer research, infectious diseases, and antibiotic resistance, potentially reducing pharmaceutical development costs by identifying failures earlier.
The pharmaceutical industry faces a persistent and costly challenge: many drug candidates that successfully bind to their intended protein targets ultimately fail because they do not produce the desired therapeutic effect. This disconnect between binding and functional efficacy costs the industry billions of euros annually and contributes to unnecessary animal testing. Now, a startup company called 4ces (search), founded by Leiden biophysicist Professor John van Noort and CEO Hidde-Jan Lemstra, aims to change this paradigm with a novel technology platform called Mech-Seq™ (search).
The core innovation lies in the technology's ability to go beyond measuring simple binding affinity. "Our technology measures how proteins bind to DNA, while also tracking changes in the structure of the DNA itself," explains Professor van Noort. "Some proteins repair DNA, for example, while others cut or join it together."
High-Throughput Functional Screening at Scale
Mech-Seq™ (search) achieves an impressive throughput of 10,000 molecules analyzed every hour, making industrial-scale screening feasible for the first time in a functional efficacy context. This capacity allows pharmaceutical companies to assess not just whether a drug candidate binds to its target, but whether it actually prevents that protein from performing its biological function.
"We can observe the effect of potential medicines in real time and see whether a drug actually prevents a protein from doing its job," says van Noort. This real-time functional readout represents a significant advance over traditional binding assays that cannot distinguish between compounds that merely occupy a target and those that meaningfully modulate its activity.
Broad Therapeutic Applicability
The technology's relevance extends across multiple therapeutic areas. Because many biological processes depend on how DNA is processed—including replication, repair, transcription, and recombination—Mech-Seq™ (search) can evaluate drug candidates targeting a wide range of DNA-related mechanisms.
"Many processes in the body depend on the way DNA is processed," van Noort notes. "Our technology can analyse medicines that target these DNA-related processes. That means Mech-Seq™ (search) has a wide range of potential applications."
The platform is positioned to support drug development in cancer research, where DNA repair and replication pathways are frequently dysregulated; infectious diseases, where pathogen-specific DNA-processing enzymes represent attractive drug targets; and antibiotic resistance, where novel mechanisms of action are urgently needed.
Economic and Scientific Impact
By enabling functional characterization of drug candidates at an early stage of development—well before clinical trials commence—Mech-Seq™ (search) offers pharmaceutical developers the opportunity to identify unsuccessful candidates much sooner. This early attrition of non-functional compounds could significantly reduce overall development costs.
Beyond cost savings, the technology provides deeper mechanistic insight into how potential medicines work at the molecular level. This understanding may allow researchers to refine and improve promising drug candidates before they advance to more expensive later-stage development, potentially increasing the probability of success in clinical testing.