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Drug Discovery Core (DDC)

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The MUSC Drug Discovery Core (MUSC DDC) is a specialized resource providing tools, facilities, and expertise for early drug discovery and chemical biology. We employ virtual and physical screening, medicinal chemistry, chemical synthesis and chemoinformatics to study of the effects and properties of small molecules and proteins. As such, we are the only drug discovery resource in South Carolina with the ability to identify high-affinity ligands for a variety of biological targets.

 

Primary Goals of the MUSC DDC

  • To facilitate the discovery of new therapeutic agents and chemical probes with the focused vision of creating new chemical entities and optimizing their structures.
  • To provide chemical and medicinal chemistry support to synthesize hits identified by physical or virtual screening, and to optimize these hits through structure-based generation of analogues.
  • To assist investigators with the creation of new intellectual property, and to collaborate with the MUSC Foundation for Research and Development (FRD) to commercialize potential therapeutics.
  • To keep MUSC abreast of and competitive in the areas of academic drug discovery, medicinal chemistry, target engagement, and cheminformatics.

 

Beeson, C., Peterson, Y. K., Perron, N., Bandyopadhyay, M., Nasarre, C., Beeson, G., Comer, R. F., Lindsey, C. C., Schnellmann, R. G., & Rohrer, B. (2021). Newly Identified Chemicals Preserve Mitochondrial Capacity and Decelerate Loss of Photoreceptor Cells in Murine Retinal Degeneration Models. Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 37(6), 367–378. https://doi.org/10.1089/jop.2020.0140

Li, X., Jiang, Y., Peterson, Y. K., Xu, T., Himes, R. A., Luo, X., Yin, G., Inks, E. S., Dolloff, N., Halene, S., Chan, S. S. L., & Chou, C. J. (2020). Design of Hydrazide-Bearing HDACIs Based on Panobinostat and Their p53 and FLT3-ITD Dependency in Antileukemia Activity. Journal of medicinal chemistry, 63(10), 5501–5525. https://doi.org/10.1021/acs.jmedchem.0c00442

Holshouser, S., Dunworth, M., Murray-Stewart, T., Peterson, Y. K., Burger, P., Kirkpatrick, J., Chen, H. H., Casero, R. A., Jr, & Woster, P. M. (2019). Dual inhibitors of LSD1 and spermine oxidase. MedChemComm, 10(5), 778–790. https://doi.org/10.1039/c8md00610e

Vose, A. D., Balma, J., Farnsworth, D., Anderson, K., Peterson, Y. K. (2019). PharML.Bind: Pharmacologic Machine Learning for Protein-Ligand Interactions. arXiv, 1911.06105. https://arxiv.org/abs/1911.06105

Kumarasinghe, I. R., & Woster, P. M. (2018). Cyclic peptide inhibitors of lysine-specific demethylase 1 with improved potency identified by alanine scanning mutagenesis. European journal of medicinal chemistry, 148, 210–220. https://doi.org/10.1016/j.ejmech.2018.01.098

Peterson, Y. K., Nasarre, P., Bonilla, I. V., Hilliard, E., Samples, J., Morinelli, T. A., Hill, E. G., & Klauber-DeMore, N. (2017). Frizzled-5: a high affinity receptor for secreted frizzled-related protein-2 activation of nuclear factor of activated T-cells c3 signaling to promote angiogenesis. Angiogenesis, 20(4), 615–628. https://doi.org/10.1007/s10456-017-9574-5

Drug Discovery Core Administration

Yuri K. Peterson, Ph.D.
Director

Dr. Peterson’s research focus is in applied pharmacologic sciences using in vitro, cell based, and in silico approaches to quantitate protein and small molecule functionality to bridge between chemical biology and pathobiology. He has experience in the experimental biology and computational modeling of protein-protein interactions, protein-ligand interactions, and hormone signaling. His research efforts have included the study of arrestins, the cytoskeleton, GPCRs, G-proteins, scaffolding proteins (like RGS and AGS G-protein regulators), prenyltransferases, methyltransferases, deacetylases, kinases, a variety of lipid binding proteins, mitochondria, and endosomes. Highlight innovations from the Peterson group include the discovery and therapeutic utility (Tat-GPR) of guanine nucleotide dissociation inhibitors, software to analyze endosome kinetics (DotQuanta), the discovery of Gi-alpha suppression in the majority of ovarian cancer patients, and methodologies to optimize virtual screening for drug discovery. Dr. Peterson’s research focus is on the application of high-content microscopy to study cellular protein kinetics, predictive bioinformatics, and targeting a variety of clinical targets.

Publications of Yuri Karl Peterson, PhD
Impact of Yuri Karl Peterson, PhD

Monika B. Gooz, M.D., Ph.D.
Biomedical Imaging

Dr. Gooz earned her MD and PhD degrees at the Semmelweis University, Budapest, Hungary, and completed her Fellowships at the Institute of Experimental Medicine of the Hungarian Academy of Sciences, Budapest, at the University of Oulu, Finland, and at MUSC. Dr Gooz is a member of several organizations including the American Physiological Society and the International Nephrology Society. She serves on the editorial board of the American Journal of Physiology: Renal Physiology, and is a special editor of The American Journal of Medical Sciences.

Ivett P. Gomez, Ph.D.
Chemical Synthesis & Lead Optimization

Facilities

The MUSC Drug Discovery Core screening facility occupies approximately 900 sq. ft. of laboratory space located in Room 420 of the Drug Discovery Building at the Medical University of South Carolina. This space is adequate to house the entire screening operation (sample prep, plate prep, bar-coding, liquid handling, plate reader), compound library, and 2 Waters LC/MS instruments. These instruments are available for individual use for a nominal fee. The computational chemistry and bioinformatics center is housed in 90 sq. ft. of laboratory space assigned to Dr. Woster (DD-422A). All data and structural information for the SC3 is stored in a secure compound database (the MUSC Vault) which is accessible to DDC staff and individual PI’s. All proprietary data are stored securely and are unavailable outside the MUSC firewall. The MUSC DDC is also well equipped for chemical synthesis, and can generate libraries of analogues based on optimization of screening hits and lead compounds.

Services

  • Virtual (computational)-based screen of SC3
  • Assisted deconvolution of data

$500

  • Virtual (computational)-based screen of SC3
  • Assisted deconvolution of data
  • Preparation of investigator-derived bioassay (96-well format)
  • Physical screen of up to 25 compounds
  • Consultation concerning proposed synthesis and hit-to-lead

Synthetic procedures would be priced separately based on cost of starting materials, number of synthetic steps, etc.

$650

  • Virtual (computational)-based screen of SC3
  • Assisted deconvolution of data
  • Preparation of investigator-derived bioassay (96-well format)
  • Physical screen of up to 100 compounds
  • IC50 determination for top 3 compounds
  • Consultation concerning proposed synthesis and limited derivatization

Synthetic procedures would be priced separately based on cost of starting materials, number of synthetic steps, etc.

$850

  • Initial consultation and assay development
  • Assisted deconvolution of data
  • Preparation of investigator-derived bioassay (96-well format)
  • Physical screen of the 1,000-member screening set
  • IC50 determination for top 10 compounds
  • Similarity search of entire SC3 for structural analogues
  • Validation screen for 75 compounds from screen and/or similarity search
  • Preliminary pharmacophore determination
  • Consultation concerning proposed synthesis and limited derivatization

Synthetic procedures would be priced separately based on cost of starting materials, number of synthetic steps, etc.

$2,250

  • Initial consultation and preparation of assay for high-throughput screening, (96-well format)
  • Physical screen of the 10,000-member screening set
  • Assisted deconvolution of data
  • IC50 determination for top 5 compounds
  • Similarity search of entire SC3 for structural analogues
  • Validation screen for 50 compounds from screen and/or similarity search
  • Preliminary pharmacophore determination
  • Consultation concerning proposed synthesis and limited derivatization

Synthetic procedures would be priced separately based on cost of starting materials, number of synthetic steps, etc.

$6,000

Synthesis & Optimization Capabilities

The MUSC DDC will design a synthetic pathway to produce hit compounds and a limited number of derivatives in high yield, and with sufficient flexibility to introduce chemical diversity. As analogues are produced and evaluated, data from biological studies are used to design more effective analogues, often guided by structure-based design. Our two-fold goal is to maximize efficacy and calculated pharmacokinetic parameters, and to generate new chemical entities (NCEs) that constitute new intellectual property. Thus, faculty and other clients are provided with potential clinical candidates that can be patented and commercialized.

Proprietary South Carolina Compound Library - SC3

As part of its mission, the MUSC has created the South Carolina Compound Collection (SC3), which is comprised of diverse molecules that can be used in biological screens to identify hits and leads for drug discovery projects. The goal in creating this library is to offer an in-house collection of validated analogues that are representative of the best compounds made by academic and industrial chemists in South Carolina. There are no restrictions on the chemical properties of these compounds (molecular weight, hydrogen bond donors and acceptors, cLogP, etc.) because the goal is to maintain a collection with high chemical diversity. Compounds are added to the collection through commercial purchases, donations of compound collections from South Carolina academic and industrial sites, and samples from researchers at MUSC and USC. All compounds are annotated and stored in the searchable SC3 database along with any associated physical and biological data.

The SC3 was founded on the original donation of 3000 compounds from retired organic chemist Charles Beam from the College of Charleston. This original donation was then bolstered by the donation of the Aeterna Zentaris Discovery Library of over 130,000 proprietary compounds and continues to expand with donations for chemists at MUSC and across the state. The SC3 average physiochemical properties are MW~400, cLogP~2, rotatable bonds ~7, ~3 proton acceptors, and 2 proton donors; however ~20% of compounds fall well outside of these averages. In terms of diversity with a threshold of 80% similarity, there are ~70,000 clusters while at 50% similarity there are ~10,000 clusters. All of the compounds are quality controlled for purity and have been characterized for general toxicity using the industry standard Alamar blue assay. Outside of MUSC, over 80% of these compounds are unknown and proprietary.

Contact Information

drugcore@musc.edu

Yuri K. Peterson, Ph.D.
Director
petersy@musc.edu

Ivett Pina Gomez, Ph.D.
Chemical Synthesis & Lead Optimization
pinaagom@musc.edu

Address

Drug Discovery Building
DD420, MSC 139
Medical University of South Carolina
70 President St.
Charleston, SC 29425