Pharmacology

Xinxin Ding, PhD, department head, Pharmacology and Toxicology, College of Pharmacy—studies enzyme function, regulation and genetics as applied to translational research for drug safety and efficacy and genetic and environmental risks for chemical toxicity. Author of nearly 200 peer-reviewed papers, book chapters and articles, he serves as associate editor for “Drug Metabolism and Disposition” and “Acta Pharmaeutica Sinica B.” Grants from the National Cancer Institute and National Institute of Environmental Health Sciences of the National Institute of Health fund his work, in part. Former chair of the NIH XNDA study section (2016-2018), he currently chairs (2018-19) Drug Metabolism and Disposition Division of the American Society for Pharmacology and Experimental Therapeutics..

Dr. Gerald (‘Gerry’) Maggiora, PhD, received a Bachelor of Science in chemistry and a PhD in biophysics from the University of California, Davis. He has more than 20 years experience in academia as a professor of chemistry and biochemistry at the University of Kansas, as well as five years as a professor in the College of Pharmacy at the University of Arizona. He has a comparable amount of experience in the pharmaceutical industry, where he served as the Director of Computer-Aided Drug Discovery for three different companies. His early work spanned numerous fields related to the development of quantum mechanical and molecular mechanics methods and their application to problems of mechanistic organic chemistry, vision, photosynthetic energy conversion, and the structural chemistry of drugs, biomolecules, and proteins. After joining the pharma industry, he directed his efforts towards the development and application of similarity and diversity methods and the analysis of biologically relevant chemical space to drug research. His recent work expands the concept of chemical space to include activity landscapes, which extend chemical spaces by including data on the activity of compounds in these spaces. This led to the notion of activity cliffs, which arise when two similar compounds exhibit significantly different activities, a phenomenon that runs counter to the well-known ‘Similarity-Property Principle’ that similar compounds tend to exhibit similar properties. Although relatively rare, activity cliffs provide significant information on structure-activity relationships that lie at the heart of drug design. He has also developed network-based representations of chemical space that circumvent many of the issues associated with the representation of these very high-dimensional spaces. He is currently continuing his work in this area. In recognition of his work in chemical informatics he received 2008 Herman Skolnik Award in Chemical Informatics presented by the Division of Chemical Information of the American Chemical Society.

Fragile-X syndrome, which includes mental and physical defects and is the most common form of inherited mental retardation. Keywords: Neurodegeneration, ALS, Aging

Christopher Hulme, PhD, focuses on small molecule drug design and developing enabling chemical methodologies to expedite the drug discovery process. Target families of particular current interest for the group are kinases, protein-protein interactions and emerging DNA receptors for indications in oncology. Such efforts are highly collaborative in nature and students will be exposed to the full array of design hurdles involved in progressing molecules along the value chain to clinical evaluation. These efforts will be aided by the group’s interest in both microwave assisted organic synthesis (MAOS) and flow chemistry. Both technologies enable ‘High-throughput Medicinal Chemistry’ (HTMC) and will be supported by similar High-throughput Purification capabilities.The group also has a long standing interest in the development of new reactions that produce biologically relevant molecules in an efficient manner. Front loading screening collections with molecules possessing high ‘iterative efficiency potential’ is critical for expediting the drug discovery process. The discovery of such tools that perturb cellular systems is of high value to the scientific community and may be facilitated by rapid forays into MCR space that can produce a multitude of novel scaffolds with appropriate decoration for evaluation with a variety of different screening paradigms.Novel hypervalent iodine mediated C-H activation methodologies is also an active area of interest. Probing the scope of the transformation below and investigating applications toward the synthesis of new peptidomimetics will be an additional pursuit in the Hulme group.

Numerous drug-induced and environmental exposure-related toxicities are the result of inter-individual variation in the ADME processes of absorption, distribution, metabolism and elimination that control the fate of these compounds from the body. Alterations in these processes provide the mechanistic basis for individual variability in response to drugs and environmental exposures. A common perception is that variability in response is due to genetic polymorphisms within the drug metabolizing enzyme and transporter genes. While there are numerous examples of these differences that play a major role in the susceptibility of genetic subpopulations for specific toxicities, the potential for transient phenotypic conversion due to temporary environmental changes, such as inflammation and disease, are often overlooked.Due to the ensuing liver damage caused by the progressive stages of NAFLD, gene expression patterns can change dramatically resulting in a phenoconversion resembling genetic polymorphisms. Because the liver plays such a key role in the metabolism and disposition of xenobiotics, this temporary phenoconversion could lead to the inability of patients to properly metabolize and excrete drugs and environmental toxicants, increasing the risk of some adverse drug reactions and environmental toxicities.

Dr. Minying Cai is currently a research professor in the Department of Chemistry and Biochemistry at the University of Arizona. She has been working in the Chemistry & Biochemistry department for more than 16 years and has more than 100 publications in the area of novel drug discovery for obesity, diabetes, cancer and pain. Dr. Cai received the Ph.D. at the University of Arizona in Biochemistry and Molecular Biophysics in 2004. Before that, she had been working in Shanghai Institute of Materia Medica; Shanghai Research Center of Biotechnology in Chinese Academy of Sciences. Dr. Cai has been working on peptide based drug discovery for more than 23 years, starting with discovery of developing anti-microbial peptide and insulin related peptide drug. Sixteen years ago, she started working on melanotropin and opioid related drug discovery. Dr. Cai's research in peptides involves highly multidisciplinary areas including chemistry and biochemistry; molecular pharmacology, molecular imaging, and cancer research, with expertise in molecular pharmacology, synthetic, organic and peptide methodology, chemical and biophysical analysis and evaluation, and in vitro and in vivo expression. Dr. Cai is currently working on several projects at the interface of chemistry, pharmacology and biology within the areas of: 1. Structure based drug design and synthesis of GPCR ligands, including developing selective hMCRs ligand; 2. Developing novel biophysics tools for molecular imaging; novel biomarker for high-throughput screening system. 3. Exploiting novel scaffold via computational chemistry for small molecule therapeutics for energy balance and cancer study; 4. Creating a nanostructured integrated platform for biodetection and imaging-guided therapy. Keywords: Drug Discovery, Melanoma Prevention, neurodegenerative diseases, Obesity and Diabetes, Melanocortin System