Multiplex platform for identifying novel bifunctional molecules

Overview

The multiplex platform developed by DynaGlu Therapeutics LLC is a revolutionary tool in the field of targeted protein degradation (TPD). This platform leverages advances in natural product-based medicinal chemistry, synthetic biology, and strain engineering to identify bioactive, patentable small-molecule therapeutics. Utilizing the NOSEEUMS™ high-throughput discovery method, it screens a vast natural product compound library against disease-relevant E3 ligases and proteins of interest (POI). The platform aims to accelerate the discovery of next-generation TPDs with superior pharmacokinetic profiles and expand our understanding of E3 ligases for multiple disease indications.

Technical specifications

• Natural Product Compound Library: A comprehensive library developed at the University of Michigan for screening against E3 ligases and POIs.
• NMR Data Modeling: Computational modeling using NMR data to integrate identified ligands into bifunctional TPD scaffolds.
• Screening and Binding Assays: Includes high-throughput screening, binding affinity tests, and SPR assays for ternary complex formation with E3 ligases and POIs.
• ADMET Profiling: Prioritization of TPD candidates based on solubility, permeability, metabolic stability, and pharmacokinetic properties.

Technology readiness level

The platform is currently at Technology Readiness Level 4, having demonstrated its capability in a laboratory setting. Moving forward, further validation will involve screening high-affinity small-molecule ligands against disease-relevant E3 ligases and POIs, with the aim of developing bifunctional TPD scaffolds that leverage the strengths of natural products.