Accelerating Hit Discovery for Hard-to-Target Proteins: A Fragment Library Approach Applied to MyD88

Fragment-based drug discovery (FBDD) offers an efficient route to explore chemical space, but critical bottlenecks remain. Commercial fragment libraries are either too large to screen routinely with biophysical methods or too small to capture sufficient chemical diversity for challenging targets. The path from fragment hits to leads demands extensive medicinal chemistry iterations with limited guidance on the most promising directions. Moreover, fragment expansions into focused compound collections lacks streamlined, integrated computational and experimental workflows, leaving a persistent gap between primary screening hits and lead series. 

Dr. Greg Makara will review BioDuro's integrated FBDD platform, which directly addresses these challenges through a rationally designed fragment library built with ChemPass' proprietary knowledge-trained technology, Surface Plasmon Resonance (SPR)-driven hit identification, and a computational expansion engine that rapidly translates confirmed hits into focused compound collections for experimental confirmation.

Dr. Shuo Gu will demonstrate this workflow on the MyD88 Toll-Interleukin receptor (TIR) domain, a high-value yet difficult-to-drug target in innate immunity implicated in inflammatory and autoimmune diseases. Long considered undruggable due to the challenging nature of its protein-protein interaction (PPI) interface, MyD88 serves as a representative example of how BioDuro’s FBDD platform can tackle hard-to-drug PPI targets across diverse therapeutic areas.  Applied to MyD88, the platform delivered high-quality fragment hits with favorable binding profiles, rapidly expanded into a focused set of candidates for experimental confirmation, demonstrating a complete, experimentally validated path from fragment screening to high-quality chemical leads.

What you will learn:

A novel integrated platform for fragment-based screening and library expansion that accelerates the early stages of drug discovery

Hit-based virtual library design and docking for efficient hit-to-lead optimization

A combined experimental and computational workflow that enables rapid hit identification for difficult-to-drug targets

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Speakers:

Shuo Gu, Ph.D.

Associate Director, Head of Computational Chemistry

BioDuro

Greg Makara, Ph.D.

CEO

ChemPass