Medicinal chemistry

Josef Vagner

Research Professor
Director, Ligand Discovery Laboratory
Research Associate Professor, Pharmacology
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 626-4179

Research Interest

Josef Vagner, PhD, is an Associate Research Professor at the University of BIO5 Research Institute and the Director of the Ligand Discovery Laboratory. Dr. Vagner is expert in the field of drug discovery and development, and he is focused on the design, synthesis, purification, characterization and screening of compound arrays.He has published over 70 original research papers and 31 patents. He is a frequent presenter at national and international meetings (American Chemical Society and Peptide Societies).Dr. Vagner designed and developed of compounds for in vivo pharmacologic applications and translation programs. He has over 25 years experience in synthesis and structural analysis of de novo ligands for various biological targets, including a recent focus on ligands targeting GPCRs and multivalent ligands. These experiences include 10 years of work in the pharmaceutical industry (Sanofi/ Selectide, Novo Nordisk, Discovery Partner International) where he specialized in combinatorial chemistry and array synthesis of small molecules. During his time in industry, he supervised teams of workers who successfully accomplished the synthesis of more than ten large libraries (with >10,000 compounds each).

David E Nix

Professor, Pharmacy Practice-Science
Professor, Pharmacy Practice-Science (Banner)
Associate Professor, Medicine
Primary Department
Contact
(520) 626-4814

Research Interest

David Nix, PharmD, joined the Department of Pharmacy Practice and Science in July, 1996. He will be teaching pharmaceutical calculations this fall as well as beginning practice and research activities. He completed a research fellowship in infectious disease pharmacotherapy in Buffalo, New York. Prior to joining the department, he worked at the Clinical Pharmacokinetics Laboratory at Millard Fillmore Hospital in Buffalo as an associate director since 1995 and as assistant director since 1989.

Laurence Hurley

Associate Director, BIO5 Institute
Professor, Medicinal Chemistry-Pharmaceutical Sciences
Professor, Medicinal Chemistry-Pharmacology and Toxicology
Professor, Cancer Biology - GIDP
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-5622

Work Summary

Laurence Hurley's long-time research interest is in molecular targeting of DNA, first by covalent binders (CC-1065 and psorospermin), then as compounds that target protein–DNA complexes (pluramycins and Et 743), and most recently as four-stranded DNA structures (G-quadruplexes and i-motifs). He was the first to show that targeting G-quadruplexes could inhibit telomerase (Sun et al. [1997] J. Med. Chem., 40, 2113) and that targeting G-quadruplexes in promoter complexes results in inhibition of transcription (Siddiqui-Jain et al. [2002] Proc. Natl. Acad. Sci. U.S.A., 99, 11593).

Research Interest

Laurence Hurley, PhD, embraces an overall objective to design and develop novel antitumor agents that will extend the productive lives of patients who have cancer. His research program in medicinal chemistry depends upon a structure-based approach to drug design that is intertwined with a clinical oncology program in cancer therapeutics directed by Professor Daniel Von Hoff at TGen at the Mayo Clinic in Scottsdale. Dr. Hurley directs a research group that consists of a team of graduate and postdoctoral students with expertise in structural and synthetic chemistry working alongside students in biochemistry and molecular biology. NMR and in vivo evaluations of novel agents are carried out in collaboration with other research groups in the Arizona Cancer Center. At present, they have a number of different groups of compounds that target a variety of intracellular receptors. These receptors include: (1) transcriptional regulatory elements, (2) those involved in cell signaling pathways, and (3) protein-DNA complexes, including transcriptional factor-DNA complexes.In close collaboration with Dr. Gary Flynn in Medicinal Chemistry, he has an ongoing program to target a number of important kinases, including aurora kinases A and B, p38, and B-raf. These studies involve structure-based approaches as well as virtual screening. Molecular modeling and synthetic medicinal chemistry are important tools.The protein–DNA complexes involved in transcriptional activation of promoter complexes using secondary DNA structures are also targets for drug design.

Christopher Hulme

Professor, Pharmacology and Toxicology
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-5322

Work Summary

The Hulme group is focused on small molecule drug design and developing enabling chemical methodologies to expedite the drug discovery process. The development of small molecule inhibitors of kinases is of particular interest.

Research Interest

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.

David T Harris

Executive Director, AHSC Biorepository
Professor, Immunobiology
Professor, Medicine
Professor, Applied BioSciences - GIDP
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-5127

Work Summary

We are involved in banking clinical specimens obtained from various patients for use in biomarker discovery and clinical therapies. Clinical therapies may include regenerative medicine, transplant or gene therapy.

Research Interest

David Harris, PhD, occupies research efforts directed at the application of (cord blood and adipose) stem cells to transplantation, regenerative medicine and tissue engineering. The difficulty in locating bone marrow donors for patients needing transplants, particularly for minority patients, led to the investigation of other potential sources of stem cells. One such source that has become a viable alternative to bone marrow is umbilical cord blood. Not only has the use of cord blood allowed more patients to go to transplant due to less restrictive matching requirements between donor and recipient, but cord blood transplants are associated with fewer post-transplant complications, such as a lower incidence and severity of graft-versus-host disease (GVHD). In 1989, he began work on the use of cord blood for transplantation, which led to the establishment of the first cord blood bank in the United States in 1992, which is currently the largest such establishment in existence. Work continues today using animal models for cord blood transplantation to explore such research areas as graft-versus-leukemia, GVHD, regenerative medicine and tissue engineering applications. However, studies performed in his lab examining the use of cord blood stem cells in regenerative medicine is now our major emphasis. Work in regenerative medicine has focused on several specific areas of interest. The first area is the use of stem cells in an ischemia/reperfusion injury model of myocardial infarction in a rat model, with positive results. Efforts are underway to understand the molecular mechanisms involved and to derive small molecule drugs in collaboration with Dr. M. Gaballa at Sun Health Research Institute. Secondly, Dr. Harris has been successful in deriving epithelial tissues in vitro that mimic corneal tissues, both morphologically and histologically. When transplanted in vivo in rabbits, the tissues are equivalent to cadaver corneas in terms of sight restoration and function. Dr. Harris and his team are currently developing a human-to-human eye model that will avoid some of the xenogeneic complications associated with the rabbit model, in conjunction with the Dept. of Ophthalmology.Third, they have successfully derived glial, astrocyte and oligodendrocyte cell types from cord blood stem cells in vitro. Currently, these cells are used to study pediatric HIV infection at the molecular level, but are also amenable to work in Parkinson’s and spinal cord injury models. Dr. Harris is now collaborating with Dr. Madhavan of Neurology to study Parkinson’s disease and with Dr. Rogers of Stanford Research Institute to study Alzheimer’s disease. Fourth, recent work has begun comparing various stem cells sources (cord blood, bone marrow and adipose tissue) for the capacity to be used in regenerative medicine. Finally, over the past year they have investigated the use of cord blood stem cells for epithelial wound healing, with the goal being the treatment of non-healing wounds and ulcers in diabetic and bed-ridden patients. It has been found that injections of bone marrow stem cells, both intravenously as well as in the wound margins, significantly reduce healing time as well as minimizing scar formation. Of interest, the age of the recipient plays a significant role in wound healing. Keywords: stem cells, regenerative medicine, biobanking

Leslie Gunatilaka

Professor, Natural Resources and the Environment
Director, Natural Products Center
Professor, Pharmacology and Toxicology
Professor, Cancer Biology - GIDP
Professor, Arid Lands Resources Sciences - GIDP
Professor, BIO5 Institute
Contact
(520) 621-9932

Work Summary

Discovery of natural products from plants and their associated microorganisms as potential drugs to treat cancer. Application of medicinal chemistry approach for structure-activity relationship studies and to obtain compounds for preclinical evaluation. Development of alternative agricultural systems for sustainable utilization of natural resources.

Research Interest

Despite many therapeutic successes, cancer remains a major cause of mortality in the US. Natural products (NPs) represent the best source and inspiration for the discovery of drugs and molecular targets. Our aim is to discover effective and non-toxic NP-based anticancer drugs. Working with NCI we have recently discovered a class of plant-derived NPs useful in cancer immunotherapy. The main focus of our current research is to utilize medicinal chemistry approach to obtain their analogues for preclinical evaluation. Leslie Gunatilaka is Professor at the School of Natural Resources and the Environment and Director of the Natural Products Center. He is also Adjunct Professor of Department of Nutritional Sciences, and a member of the Arizona Cancer Center. He is a member of several professional societies, editorial boards, and pharmaceutical company advisory groups. He is a Fellow of the Academy of Sciences for the Developing World (TWAS), Italy, and the National Academy of Sciences, Sri Lanka. Dr. Gunatilaka has over 200 peer-reviewed publications and book chapters and over 150 communications in natural product science to his credit. He is the recipient of the Sri Lankan Presidents’ gold medal for “creating a center of excellence in natural products research at the University of Peradeniya, Sri Lanka” (1987), CaPCURE award for “dedication to ending prostate cancer as a risk for all men and their families” (2000), Research Faculty of the Year Award of the UA College of Agriculture and Life Sciences (2003), the UA Asian American Faculty, Staff and Alumni Association Outstanding Faculty Award (2005), and the UA Leading Edge Researcher Award for Innovative Research (2012). He has delivered over 100 invited lectures worldwide and was the Chief Guest and Plenary Lecturer at the International Herbal Medicine Conference held in Sri Lanka (2005), and the Keynote Speaker and the Guest of Honor at Chemtech-2007, an International Conference organized by the Institute of Chemistry, Ceylon. His current research interests include discovery, identification of protein targets, and structure-activity relationship (SAR) studies of natural product-based drugs to treat cancer, neurodegenerative, and other diseases from plants, and plant- and lichen-associated microorganisms, maximization of chemistry diversity and production of microbial and plant secondary metabolites, and scientific investigation of medicinal plants and herbal supplements. Keywords: Natural Product-Based Drug Discovery, Medicinal Chemistry, Cancer Immunotherapeutic Agents

Vijay Gokhale

Associate Research Professor
Primary Department
Department Affiliations
Contact
(520) 626-4224

Work Summary

Vijay Gokhale's work includes the use of medicinal chemistry in the development of small molecule therapeutics for neuropathic pain, idiopathic pulmonary fibrosis (IPF), and acute lung injury and cancer.

Research Interest

I am a senior research scientist and oversees medicinal chemistry research at BIO5 Institute's drug discovery initiative. I oversee group of medicinal chemistry involved in the development of small molecule therapeutics for idiopathic pulmonary fibrosis (IPF), neuropathic pain, acute lung injury and cancer. I am co-founder of Reglagene and Regulonix - two biotech companies with startup technology from the University of Arizona. I have 15 years' experience in medicinal chemistry with expertise in translational drug development. I am also a co-inventor of small molecules targeting hTERT and MYC for the treatment of glioblastoma, melanoma, lymphomas and prostate cancer. Our work in the area of neuropathic pain has led to successful funding from Tech Launch Arizona and will result in STTR funding from NIH.

Brian L Erstad

Department Head, Pharmacy Practice-Science
Professor, Pharmaceutical Sciences
Member of the Graduate Faculty
Professor, BIO5 Institute
Primary Department
Contact
(520) 626-4289

Work Summary

Brian Erstad’s research interests pertain to critical care medicine with an emphasis on patient safety and related outcomes research.

Research Interest

Brian L. Erstad, PharmD, FCCM, is currently a tenured professor and head of the Department of Pharmacy Practice and Science. He is also a center investigator for the Center for Health Outcomes and PharmacoEconomics Research and a co-director for the Arizona Clinical and Translational Research Graduate Certificate Program. His clinical responsibilities are performed at Banner-University Medical Center Tucson.Dr. Erstad’s research interests pertain to critical care medicine with an emphasis on patient safety and related outcomes research. He has authored more than 150 peer-reviewed articles and book chapters.Dr. Erstad has served on the board of directors of the American Society of Health-System Pharmacists and on numerous committees and task forces for other organizations including AHRQ, USP, Society of Critical Care Medicine and the American College of Chest Physicians. He is currently an ad hoc member of the FDA’s Drug Safety and Risk Management Advisory Committee, a steering committee member of the United States Critical Illness and Injury Trials (USCIIT) Group, and treasurer of the American College of Clinical Pharmacy.

Nathan J Cherrington

Professor, Pharmacology and Toxicology
Associate Dean, Research and Graduate Studies - College of Pharmacy
Director, Southwest Environmental Health Science Center
Professor, Public Health
Professor, Clinical Translational Sciences
Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-0219

Research Interest

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.

Minying Cai

Research Professor
Research Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Department Affiliations
Contact
(520) 621-8617

Work Summary

Peptides and proteins play a vital role in almost every cellular process in living organisms. Our research discovers and determines structural information on peptides and proteins to design drugs to more effectively treat human disease.

Research Interest

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