Co-Director (Med Chem): Chad Bennett, PhD
Co-Director (HTS): Blake Peterson, PhD
Technical Director (HTS): Meng Wu, PhD
Biologically Active Small Molecules Are Our Business
The Drug Discovery Shared Resource (DDSR) integrates the expertise of multiple disciplines, including synthetic and process chemistry, instrumental analysis, chemical biology and molecular pharmacology, to provide medicinal chemistry and high-throughput screening support to investigators at the OSUCCC – James as well as to other academic and commercial institutions.
The goal of the DDSR is to provide investigators with multiple different aspects of medicinal chemistry and small molecule screening services, including chemistry consultation, design and synthesis of new molecules of biological interest, sample purity analyses and custom syntheses of known agents. We offer high-throughput screening and high-content screening of small molecule libraries against a wide range of biological assays and targets. In collaboration with other OSUCCC – James Shared Resources, the DDSR aims to translate basic science findings from investigators into small-molecule, target protein degraders, and antibody drug conjugate agents for testing individual hypotheses, adding an important dimension in translating basic science to the clinic.
Services
The medicinal chemistry core of the DDSR (DDSR-MC) offers consultation and synthetic medicinal chemistry. Staff of DDSR-MC work with investigators to design new derivatives of lead structures with the goal of improving biological properties, such as potency, efficacy and bioavailability. We scale-up agents to support more in-depth studies, such as in vivo efficacy and pharmacokinetic/pharmacodynamics studies. If mechanistic probes are needed, the DDSR will collaborate with investigators to design and synthesize tool molecules for probing biological pathways. Our services include:
- Custom synthesis of agents not available from commercial sources: Chemists of the DDSR consult with investigators to determine the potential to synthesize small molecules of interest and carry out the synthesis of target compounds. DDSR also develops affinity probes and targeted protein degraders for mechanistic interrogation. These agents enable proof-of-concept in vitro and/or in vivo experiments testing hypotheses in preclinical studies.
- Commercially available small molecules: Staff of DDSR-MC consult with investigators regarding the availability, stability and purity of chemical agents available from vendors. We conduct nuclear magnetic resonance spectroscopy, mass spectrometry and other analyses to verify the identity and/or purity of chemical agents.
- Structure Activity Relationship (SAR) Analysis and Lead Optimization. DDSR will evaluate drug-like characteristics of a lead structure, such as lipophilicity, target selectivity, metabolic stability, and pharmacokinetics that are important for drug development. With these considerations, new derivatives are designed and synthesized to develop a structure activity relationship (SAR). SAR analysis is used to understand what structural elements of a molecule are key for the desired biological activity, guiding the design of new derivatives of existing lead compounds for improved potency, efficacy, safety, and bioavailability. Biological evaluation is carried out in collaboration with other SRs and PI’s labs as needed.
The high-throughput screening (HTS) of the DDSR offers access to libraries of diverse small molecules, high-content screening using confocal imaging and luminescence-based high-throughput screening of these libraries against biological pathways and proteins. Our services include:
- Assay adaption and development: Assays provided by investigators can be adapted to HTS on multi-well plates or developed from existing methods as supported by statistical validation.
- High-throughput screening: Pilot screening, primary screening and secondary screening against target proteins with a wide variety of readouts.
- High-content screening: Confocal microscopy-or flow-cytometry-based primary and secondary screening, against cellular phenotypes or specific expressed target proteins.
- Hit validation: Verification of compound activity using replicated dose-response studies.
- Collections of plated compounds: Copies of libraries, collections of cherry-picked compounds and compound plates arrayed for dose-response studies.
- Data analysis: Quantitative assessments of HTS data and high-content imaging data
- Grant writing assistance: Letters of support, descriptions of facilities and equipment, and consultation on generation of preliminary data for grant applications.
- Supporting services: Facilitating access to experts in medicinal chemistry (e.g., hit-to-lead and lead optimization studies), drug development (PK/PD) and translational research for preclinical studies and planning for clinical trials.
- Project management: Electronic notebooks and data management strategies.
More information about capabilities and services of the DDSR-HTS can be found at https://u.osu.edu/highthroughputscreeningcore.
For more information about the Drug Discovery Shared Resource, please email Chad.Bennett@osumc.edu, Peterson.1119@osu.edu or Meng.wu@osumc.edu.