Cube Biotech & X-Chem Partner to Enable DNA-Encoded Library Screening of NativeMP-Stabilized Membrane Proteins

Cube Biotech and X-Chem recently announce the successful conclusion of Project DEL-MP, a collaborative initiative demonstrating that copolymer-stabilized membrane proteins are not only suitable for DEL screening, they also open up completely new possibilities for even the most challenging targets.

The groundbreaking project combined Cube Biotech’s proprietary NativeMP copolymer technology — which enables the stabilization of functional membrane proteins in near-native conformations — and X-Chem’s world-class DEL platform and expertise in complex target screening. As a result, new avenues are now open for drug discovery against some of the most challenging targets in biomedical research.

“For years, the field has questioned whether DEL screening could be extended to membrane proteins,” said Barbara Maertens, COO and co-founder of Cube Biotech. “With Project DEL-MP, we’ve proven that not only is it possible — it’s optimal. NativeMP preserves native conformation, protein functionality, and accessibility of extracellular pockets — a trifecta for meaningful hit discovery.”

“Membrane proteins are some of the most important targets in drug discovery, yet they have been among the most difficult to screen effectively,” added Matt Clark, CSO of X-Chem. “By combining Cube Biotech’s NativeMP technology with X-Chem’s DEL screening platform, we have shown that high-quality, data-driven discovery is now possible for these challenging targets. This collaboration validates a new path forward, one that expands the impact of DEL and opens opportunities for innovation across many therapeutic areas.”

DEL-MP is a joint proof-of-concept and platform validation program designed to:

• Demonstrate robust DEL hit discovery against selected membrane proteins targets from different classes, and stabilized in a subset of different NativeMP copolymers
• Benchmark NativeMP proteins, including GLP1R, EGFR, TNF, P2YR11 and P2X4, revealed highly productive DEL screen readouts with enriched, target-selective compounds suitable for off-DNA synthesis and assays, independent of type NativeMP copolymers used for stabilization
• Demonstrate seamless automation compatibility for scalable DEL screening workflows using high-throughput instrumentation

Results from feasibility experiments, conducted on X-Chem’s screening platform, show promising results for NativeMP-stabilized membrane protein targets — maintaining binding competency and structural fidelity over extended incubation periods.

Cube Biotech specializes in the purification, stabilization, and functional screening of membrane proteins, offering solutions that power drug discovery campaigns around the globe — for the first time, also as a fully automated workflow. With the NativeMP copolymer technology, Cube enables native-like solubilization of even the most fragile targets — including GPCRs and multi-pass transporters — without the use of harsh detergents. Cube Biotech, with the strategic backing of ARCHIMED, is committed to advancing the full protein research value chain — from discovery to delivery. Learn more: www.cube-biotech.com

X-Chem is a global leader in data-driven drug discovery, partnering with biopharma innovators to tackle the most challenging targets. Its integrated platform combines DEL screening, medicinal chemistry and advanced data analytics to uncover deeper insights, reveal untapped opportunities and accelerate the delivery of breakthrough small-molecule therapeutics. Discover what’s possible at www.x-chemrx.com.