Leaders

	Menachem Shoham, PhD Associate Professor, Biochemistry mxs10@case.edu
	Anthony J. Berdis, PhD Assistant Professor, Pharmacology ajb15@case.edu

Summary

Cancer Center members in this focus group are engaged or plan to be engaged in drug discovery to combat various forms of cancer. This will include cell-based assays to screen for potential drugs, as well as structure-based approaches to derive at "hit" compounds, which are candidates for further development into "lead" compounds.

This focus group will provide a platform for the interaction between cancer biologists and structural biologists.

Structure-Based Drug Design

The target protein has a known crystal or solution NMR structure

In this case one can screen kits of small-molecule compounds, available from NCI and commercial sources for binding to the target protein. High-affinity binders are subsequently co-crystallized with the target protein in order to gain understanding how to modify the compound to increase the affinity.

Alternatively, the initial screening can de done by in silico docking into the active site of the target protein. The most promising compounds are then subjected to binding assays and co-crystal structure determination.

The target protein is not known or no 3-D structure is available

If one or more small-molecule inhibitors of the target protein are known (for example a peptide) one can use this inhibitor to define a pharmacophore, which forms the basis for in silico screening against a database of commercially available compounds. The top hit compounds are purchased to perform binding and activity assays.

Structure-activity studies are subsequently carried out with the help of a medicinal chemist in order to improve the efficacy of the compound. Once a "lead" compound has been identified further studies are necessary to establish bioavailability, pharmacokinetics and toxicology prior to clinical trials. Since these studies are costly the project usually moves at this stage into the commercial arena with substantial investment from venture capitalists.

Members

Anthony J. Berdis, PhD
Assistant Professor, Pharmacology
ajb15@case.edu

David Danielpour, PhD
Professor, General Medical Sciences (Oncology)
dxd49@case.edu

Chris G. Dealwis, PhD
Associate Professor, Pharmacology, Proteomics
cxd114@case.edu

Jeffrey L. Duerk, PhD
Professor, Radiology, Biomedical Engineering
duerk@case.edu

Stanton L. Gerson, MD
Director, Case Comprehensive Cancer Center
Professor, Medicine-Hematology/Oncology
slg5@case.edu

Sanjay Gupta, PhD
Professor, Urology
sanjay.gupta@case.edu

Subrata Haldar, PhD
Associate Professor, Pharmacology
shaldar@metrohealth.org

Henry B. Koon, MD
Assistant Professor, Medicine-Hematology/Oncology
henry.koon@case.edu

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John J. Letterio, MD
Professor, Pediatric Hematology/Oncology
john.letterio@UHhospitals.org

Lili Liu, MD, PhD
Associate Professor, Medicine-Hematology/Oncology
lxl32@case.edu

Saurav Misra, PhD
Assistant Professor, Molecular Cardiology
misras@ccf.org

Cheng-Kui Qu, MD, PhD
Associate Professor, Medicine-Hematology/Oncology
cxq6@case.edu

Menachem Shoham, PhD
Associate Professor, Biochemistry
mxs10@case.edu

George R. Stark, PhD
Professor, Molecular Genetics
starkg@ccf.org

Yanming Wang, PhD
Associate Professor, Radiology
yanming.wang@case.edu

Vivien C. Yee, PhD
Associate Professor, Biochemistry
vcy2@case.edu