The Fisher Drug Discovery Resource Center
The Fisher Drug Discovery Resource Center at The Rockefeller University
A shared academic facility providing access to compound libraries, high-throughput screening, and drug discovery infrastructure — accelerating the path from molecular insight to therapeutic candidate.
As part of the creation of the Zachary and Elizabeth M. Fisher Fund for Translational Research in Alzheimer’s and Neurodegenerative Disease at The Rockefeller University in 2022, the university’s High Throughput and Spectroscopy Resource Center officially became the Fisher Drug Discovery Resource Center (DDRC).
Fraser Glickman, PhD
Since its establishment in 2003, the DDRC has become one of the foremost academic facilities for early-stage drug development. Directed since 2008 by Fraser Glickman, PhD, a leader with over three decades of industry experience in drug discovery, the DDRC operates on an open-access model. Scientists from The Rockefeller University and other institutions receive hands-on training to identify and optimize compounds targeting precise molecular pathways. A dedicated staff with extensive expertise in biochemistry, bioassay design, and lab automation supports all stages of project development from hit identification to lead optimization and data analysis, helping researchers move studies forward at the highest standard of efficiency and reliability.
The DDRC supports five main research areas:
- Developing assay cascades for drug discovery projects
- Miniaturized assay development
- High-throughput screening
- Identifying compounds for drug discovery or biomedical research
- Measuring the kinetics and thermodynamics of biomolecular interactions
Library and Screening Infrastructure
The heart of the DDRC is a chemical library of over 638,000 molecules, representing a wide range of drug-like compounds—such as natural products, low molecular weight screening compounds, pharmacologically active compounds, clinically used compounds, and compound fragments. This is a highly selective collection curated through algorithms rooted in clustering, diversity analysis, and molecular property calculations.
Understanding how molecules interact with their targets is key to driving therapeutic innovation. To that end, the DDRC provides access to powerful state-of-the-art instruments and techniques, including:
- Automated liquid-dispensing systems for precise pipetting
- Advanced microplate readers and analytical systems
- Surface Plasmon Resonance
- Microscale Thermophoresis
- Temperature-Related Intensity Change
- Spectral Shift Analysis
- Circular Dichroism Spectrometry
- Thermal Melt Analysis
- Isothermal Titration Calorimetry
Scientific Impact
The DDRC has played a critical role in several high-impact research efforts, contributing to the discovery of both therapeutic candidates and fundamental molecular insights. Key DDRC-supported studies include:
- Inhibitors of SARS-CoV-2 NSP14 RNA methyltransferase: In a collaboration with the Tuschl Lab at The Rockefeller University, the DDRC screened over 430,000 compounds to discover small-molecule inhibitors targeting NSP14, a critical viral enzyme for the replication of SARS-CoV-2 (the virus that causes COVID-19). This work led to a paper published in Nature in 2025.
- Human cGAS-specific inhibitors: Researchers developed small-molecule inhibitors targeting human cGAS, a DNA-sensing enzyme linked to inflammatory responses. These inhibitors were shown to suppress interferon expression triggered by double-stranded DNA—an advance in understanding innate immune regulation. This work led to a paper published in Nature Communications in 2019.
- Amyloid-beta–fibrinogen interaction inhibitors: DDRC researchers contributed to a study demonstrating that targeting the interaction between amyloid‑beta and fibrinogen in Alzheimer’s disease models restored normal clotting and rescued cognitive function in mice. This work was featured in the Journal of Experimental Medicine in 2014.
- Allosteric inhibitor of soluble adenylyl cyclase (sAC): The DDRC supported the discovery of LRE1, a specific and allosteric inhibitor of sAC, opening new avenues for regulating cAMP signaling in a variety of biological contexts. This work was published in Nature Chemical Biology in 2016.
- Hedgehog acyltransferase inhibitors: Researchers developed inhibitors of Hedgehog acyltransferase, providing a chemical tool for modulating Hedgehog signaling—a pathway implicated in development and cancer biology. This study was published in Nature Chemical Biology in 2013.
A Shared Commitment to Translational Research
The DDRC has recently implemented important additions to its capabilities:
- 50,000 new compounds were added to its library
- A new isothermal calorimeter and a new Integra WellJet were purchased to support enhanced screening and binding analysis
Building on its technical and strategic expertise, the DDRC continues to accelerate drug discovery and therapeutic innovation. By equipping scientists with mechanistic insight and cutting-edge resources, the DDRC removes barriers to discovery, empowering processes that remain essential to translational research conducted in the labs supported by the Fisher Center Foundation and beyond.
