The Department of Chemistry is excited to host Dr. Charles Hendrick, G'17 (Johnson & Johnson Innovative Medicine) on Friday, April 25, 2025 for a departmental seminar.
"High-Throughput Chemistry to Accelerate Modality Agnostic Drug Discovery"
Direct-to-biology strategies, involving synthesis of large libraries at micro-scale and assaying them as unchromatographed mixtures, have emerged as an attractive high-throughput parallel synthesis approach to reduce design-make-test cycle times by eliminating slow and costly chromatographic purification. As one part of a broader high-throughput chemistry platform, these capabilities allow faster execution, analysis, and design iteration while reducing consumption of precious synthetic intermediates to greatly accelerate drug discovery programs. Supported by developments in automated synthesis, parallel chemistry, and molecular pharmacology, direct-to-biology approaches can be applied across modalities and in diverse biochemical and cellular assays. This presentation, on behalf of the Chemistry Capabilities, Analytical and Purification group, will highlight one example, a platform to accelerate optimization of proteolysis targeting chimeras (PROTACs) using a direct-to-biology approach focusing on linker effects. A large number of linker analogs─with varying length, polarity, and rigidity─were rapidly prepared via three-step telescoped reaction sequence, without chromatographic purification, and characterized in four cell-based assays. The dataset informs on linker structure–activity relationships (SAR) for in-cell E3 ligase target engagement, degradation, permeability, and cell toxicity. Continued innovation in high-throughput chemistry and direct-to-biology enables more complex synthetic sequences to be executed in direct-to-biology mode with hit-validation through microscale purification, increasing capabilities to address emerging medicinal chemistry challenges.
Seminar hosted by GCC and Prof. Qiu Wang
