Leading state-of-the-art chemistry technologies centers focus on collaborative research with St. Jude investigators to further our understanding of biological mechanisms that result in childhood diseases. The overarching goal is to translate this knowledge into new therapeutic opportunities. CBT centers form an integrated pipeline to bring chemistry to medicine at St. Jude. Collaborative projects involve a close partnership between the laboratory and the participating centers.
Unlike shared resource centers, we are, by design, a collaborative department that develops innovative chemical and chemoinformatic solutions to tackle fundamental problems in biology and medicine. The collaborative centers possess chemical synthesis, high-throughput and high-content screening, analytical, pre-clinical, and computational capabilities that mirror leading biotech/pharma operations and are rarely accessible at academic institutions.
CM stores and maintains the St. Jude compound library in optimal
conditions to deliver compounds in various formats as required by different researchers.
HTB develops robust cell-based and biochemical assays to test thousands of compounds in high-throughput screening using state-of-the-art robotic systems
LDI uses chemo-centric informatics to virtually screen thousands of molecules, dock ligands into target structures, and develop models for complex data analysis
CBC selects biologically active candidates by testing them in cell-based assays and develops tools like PROTACS, molecular glues, and photoaffinity probes.
MCC develops potent and selective small molecules supporting post-screening structure-activity relationships studies to improve the chemical properties of lead candidates.
ATC utilizes bioanalytical methods to understand pharmacokinetics of lead compounds and develops formulations for pre-clinical candidates.
Centers in Action: A CBT Library
With one of the largest compound collections in academia, containing over 600,000 carefully annotated small molecules, CBT is paving the way in drug-discovery research. Gisele Nishiguchi, the compound collections specialist, leads a team of 4 scientists from different CBT centers who curate the collection. Currently, the collection contains small molecules from vendors, compounds from in-house parallel synthesis, analogs of internal medicinal clinical candidate projects, focused libraries designed for specific targets or target classes, fragments, natural products, approved drugs, and chemical probes from literature. It is organized in a ‘library of libraries’ design, where subsets can be screened independently according to a project’s specific needs. The team’s objectives are to leverage and expand the existing library by acquiring compounds enriched for biological activity and new approved drugs and probes. The team’s current collaborations include creating a molecular glue library, both via vendors and in-house synthesis, with multiple faculty across St. Jude and CBT. Recently, the team made available a Mechanism of Action Library (MOA), which consists of 2050 small molecules, covering over 1,000 primary gene targets.
Selected publications
A bromodomain-independent mechanism of gene regulation by the BET inhibitor JQ1: direct activation of nuclear receptor PXR
Huber AD, et al. Nucleic Acids Res 2024
Selective CK1α degraders exert antiproliferative activity against a broad range of human cancer cell lines
Nishiguchi G et al. Nat Commun, 2024
A CRISPR-drug perturbational map for identifying new compounds to combine with commonly used chemotherapeutics
Lee HM, et al, Geeleher. Nature Comm 2023
Patient-derived models recapitulate heterogeneity of molecular signatures and drug response in pediatric high-grade glioma
Chen H et al. Nat Commun, 2021
Identification of Potent, Selective, and Orally Bioavailable Small-Molecule GSPT1/2 Degraders from a Focused Library of Cereblon Modulators
Nishiguchi G et al. J Med Chem, 2021
Evaluating and evolving a screening library in academia: the St. Jude approach
