The race to identify drug targets is often slowed by delays in protein expression, purification and characterization – bottlenecking therapeutic development.
Kinase proteins are no exception. Traditional workflows often suffer from inefficiencies that stall progress in preclinical and translational research. As therapeutic timelines tighten, there's growing urgency to streamline protein production and data acquisition.
This application note presents a next-generation approach to drug discovery – combining AI-guided structural design with rapid, automated digital microfluidics-based screening workflows that optimize protein expression. Researchers can obtain purified proteins in 48 hours for SPR kinetic analysis, enabling target characterization in just five days.
Download this free application note to discover:
- How to go from DNA to SPR data in record time
- Proven strategies to streamline protein expression and rapid screening
- Practical methods to reduce early discovery timelines and accelerate validation
Application Note
Accelerated Kinase Drug Discovery:
From DNA to Protein Characterization
in 5 Days
Sunidhi C. Shetty1, Kundan Sharma1, Ruben Tomás1,
Narasimha Murthy Bandaru2, Marco Manni1, Stephanie Reikine1,
Anna Moberg2, and Yvonne Tan1
1Nuclera Ltd. Cambridge, UK
2Cytiva™ Sweden AB, Uppsala, Sweden
Introduction
The rapid pace of drug discovery demands efficient technologies to accelerate target
identification, characterization, and optimization.
A major bottleneck in early drug discovery is the slow, inefficient expression of viable drug
targets using traditional cell-based methods, which are hindered by solubility, stability, and
purification challenges. Nuclera’s eProtein Discovery™ system integrates AlphaFold-driven
modeling, digital microfluidics, and cell-free synthesis, enabling functional protein production in
48 hours and expediting target availability.
Once expressed, confirming kinetic analysis and structure-activity relationships (SAR) is critical
for selecting and refining drug candidates. Biacore™ surface plasmon resonance (SPR) provides
real-time drug-target interaction data, delivering insights into binding kinetics, affinity, and
specificity, all essential for lead optimization and efficacy assessment1-3.
Bruton’s Tyrosine Kinase (BTK) is critical in B-cell receptor signaling and a key target in leukemia,
lymphoma, and autoimmune diseases. First-generation inhibitors like ibrutinib face resistance
(e.g. C481S) and off-target effects4. Second-generation inhibitors (acalabrutinib, zanubrutinib)
improve selectivity but still struggle with resistance and bioavailability issues5,6. Non-covalent
inhibitors (fenebrutinib, vecabrutinib) retain activity against C481S mutants but bind BTK
reversibly, requiring detailed kinetic characterization to assess their therapeutic potential7.
This study presents an integrated solution by Nuclera and Cytiva™, accelerating BTK-inhibitor
screening from DNA to functional characterization in five days. The eProtein Discovery™ system
enables high-yield Avi-tagged BTK expression, while Biacore™ SPR delivers detailed kinetic and
functional insights. This streamlined workflow enhances drug target production, accelerates
screening, and enables faster, data-driven decision-making in kinase drug discovery.
www.nuclera.com
