Acquire, develop, and deploy state-of-the-art chemistry capabilities to advance research at St. Jude towards the discovery of breakthrough treatments for catastrophic pediatric illnesses.
The CBT Chemistry Centers consist of three highly integrated centers that collectively provide state-of-the-art chemical probe design, synthesis, and evaluation of capabilities to support research at St. Jude.
Chemical Biology Center (CBC) applies advanced chemical biology methods to develop sophisticated chemical tools designed to map and interrogate disease-related biological pathways. The CBC chemical toolbox includes PROTACs, molecular glues, pull-down, photoaffinity, and imaging probes. The center has experience developing and utilizing biochemical assays, including fluorescence polarization (FP), time-resolved fluorescence energy transfer (TR-FRET), AlphaScreen, and cell-based assays such as CellTiter-Glo, Caspase-Glo, and alamarBlue.
Medicinal Chemistry Center (MCC) focuses on identifying and developing potent and selective small molecules to investigate disease-related biological targets in cells and in vivo preclinical models. Typically, the center would help researchers to find relevant literature disclosed probes (conferences, scientific journals, or patents) and arrange for their purchase or synthesis if commercially unavailable. In addition, the center would engage in a hypothesis-driven research effort to provide novel chemical probes for targets where such molecules do not exist. MCC would facilitate forming multidisciplinary projects, including core teams, multiple PIs, and other collaborative centers for these efforts.
Our team will drive the projects from hit generation and validation (e.g., HTS, fragment screening, rational design) through lead optimization relying on structure-based drug discovery, chemoinformatics, and ADME data, to delivering robust in vitro/ in vivo chemical probes.
Analytical Technologies Center (ATC) provides an extensive battery of assays designed to evaluate compound chemical, biophysical and ADME properties. These include sample purity and integrity, aqueous solubility, permeability, microsomal and plasma stability, simulated gastric fluid (SGF) stability, PBS stability, plasma/tissue protein binding, and P-gp/BCRP efflux, as well as in vivo pharmacokinetic parameters such as drug plasma and brain unbound concentrations. The center also develops highly customized bioanalytical methods, formulations for in vivo studies, mass spectrometry-based biochemical assays, and tissue imaging. In addition, the center has extensive experience in natural product extract fractionation, high throughput library purification, and structure determination.
The Chemistry Centers also routinely assists collaborators by coordinating work with other CBT centers, providing training, consultation, and help with defining project strategy, writing grant applications, patents, and manuscripts for publication. Our projects are generally highly collaborative, involving an iterative exchange of material and data with research labs that often last months, if not years.
Zoran received his Ph.D. in organic chemistry in 1995 from the University of Leeds, UK. That same year he joined Organon UK and then continued his medicinal chemistry and drug discovery career as medicinal chemistry director and research fellow within Schering-Plough, Merck, and Eli Lilly. Over this period, Zoran has been fortunate to contribute to and direct teams that delivered multiple clinical candidates over a range of therapeutic areas, including neuro-oncology, neurodegeneration, psychiatry, and pain. In the process, he has authored >80 peer-reviewed publications, patents, book chapters and edited two books on drug discovery topics. Zoran served on various drug discovery committees and advisory boards, most recently the Steering Committee of the AARC Chemistry in Cancer Research and Scientific Committee for the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics conference. Since joining St. Jude in October 2016, Zoran’s research focus includes developing small molecule protein degraders and epigenetic modulators for the treatment of pediatric cancers such as medulloblastoma, neuroblastoma, acute lymphoblastic, and myeloid leukemia.
Zoran Rankovic, PhD - Director
St. Jude Children Research Hospital