Dr. Victor J. Hruby is a Regents Professor in the Department of Chemistry and Biochemistry at the University of Arizona. He received his PhD at Cornell University in Theoretical Organic Chemistry and did a Postdoctoral studies with Nobel Laureate Vincent du Vigneaud. He has been a professor at University of Arizona since 1968 where he has joint appointments in the Neuroscience Program, Medical Pharmacology, and Bio5 among others. Dr. Hruby’s research interests are in the chemistry, biophysics, molecular pharmacology, molecular biology of peptide hormones and neurotransmitters and their receptors, transduction systems and in the design, synthesis and bio evaluation of novel ligands for the treatment of degenerative diseases.

Professor Hruby’s research has been primarily in the chemistry, conformation-biological activity relationships, molecular mechanisms of information transduction and of molecular diseases associated with peptide hormones and neurotransmitters and their receptors that modulate health, disease and human behavior. Specific methods and approaches used in this research include: de novo design of biologically active peptides and peptidomimetics; peptide and peptidomimetic synthesis; asymmetric synthesis; design and asymmetric synthesis of novel amino acids; computational chemistry; conformational analysis using NMR, X-ray crystallography and other biophysical tools; combinatorial chemistry; conformation-biological activity relationships; the design, synthesis and biological evaluation of peptide and peptide mimetic ligands that affect pain, addictions, feeding behaviors, pigmentation, sexual behavior and motivation, glucose homeostasis, cancer and other biological effects; peptide mimetic design; and the structure-function of G-protein coupled receptors. The Hruby group also is developing new synthetic methodologies for the assembly of multimeric ligands for the detection and treatment of pain, cancer and other diseases; a new approach to design of ligands for disease states involving the concept of overlapping pharmacophores to address several receptors simultaneously in a single molecular ligand. Professor Hruby has published over 1000 articles, reviews, chapters, commentaries and editorials and has over 25 patents and patent filings. Victor Hruby has received numerous awards and honors, including a Guggenheim Fellowship (1984), the Alan E. Pierce Award (now the Merrifield Award) (1993), a Senior Humboldt Fellowship (1999-2000), the American Chemical Society Ralph F. Hirschmann Award (2002), the Arthur C. Cope Scholar Award (2009), the Murray Goodman Award (2011), the ACS Medicinal Chemistry Hall of Fame (2012) and the Meienhofer Award (2012).

Dr. Carsten Detering obtained his PhD in Physical Chemistry from the Freie Universitaet Berlin in Germany in 2001. He did his Post Doc at the University of Washington in Seattle where he worked on the application of docking software for nucleic acid drug targets and rational design of new inhibitors for a malaria project. In 2005 he came to BioSolveIT in Germany as an Application Scientist first, later filling the position of Senior Key Account Manager and Executive VP of Sales, North America, before moving back to Seattle as CEO of BioSolveIT Inc, the north American subsidiary of BioSolveIT.

He worked on the application of docking software for nucleic acid drug targets and rational design of new inhibitors for a malaria project.

Thorsten Nowak completed his PhD from the University of Cambridge (UK) in the areas of aldol methodology and natural product synthesis. In 1996 he joint AstraZeneca where he worked on all stages of drug discovery from target to candidate selection in medicinal chemistry as team leader and project manager. His keen interest in new technologies motivated a career move from big pharma to platform technology business in 2012 when he joint C4X Discovery. In his current role he is responsible for all internal drug discovery projects at C4X Discovery as well as continued development of the technology in the context of application to drug discovery.

The spotlight in drug discovery and design has been firmly centred on “quality” and “efficiency” in an endeavour to improve productivity and reduce high development attrition rates. In particular, much attention has been focused on measured and predicted drug property optimization because this is expected to significantly impact both the quality and the efficiency of drug design. With such a dominating focus, it is right to ask if other important aspects of drug design are being generally overlooked by the medicinal and computational chemistry community. This presentation aims to make a case for the increasingly clear importance (and therefore necessary adoption) of conformational design in harmony with property optimization. It is argued that the impact of creatively applied conformational design based on a validated experimental foundation will lead to a number of benefits and can be far reaching. For example, limiting shape diversity whilst gaining a deep understanding of shape giving structural features presents a complementary approach to property based design. It will lead to a tighter integration of the highly complementary medicinal and computational chemistry workflows. And importantly, it will provide undoubtedly a driver to re-invigorate the development and creative exploitation of experimental methods aimed at describing and predicting the conformational behaviour of small molecules in solution. Hence, conformational design based on experimental evidence offers new drivers for innovation in drug discovery.

Concepción González-Bello has obtained her Ph.D. at the University of Santiago de Compostela (USC, Spain) in 1994. She did two predoctoral stays in the University of Gent (Belgium) with Prof. Vandewalle and in the Scripps Research Institute (USA) with Prof. Nicolaou. After three years of postdoctoral stay in the University of Cambridge (UK) with Prof. Chris Abell, she joined USC as an Assistant Professor, and was promoted to Associate Professor in 2003 and obtained the Spanish habilitation to full Professor in 2011. She is a member of the ChemMedChem International Advisory Board and has published about 50 papers in reputed journals.

Research group: Biological Chemistry and Supramolecular. Design and synthesis of new antibiotics and herbicides, Study of biological processes by molecular dynamics, Solid Phase Chemistry: Combinatorial chemistry, development of processes catalyzed by organo-metallic compounds.

Dr. Kal Ramnarayan (Dr. Ram) is the Founder, President, Chief Scientific Officer of Sapient Discovery. Previously, Dr. Ramnarayan Co-founded Structural Bioinformatics, Inc and Cengent Therapeutics, Inc. As part of the senior management team, he participated in raising more than US$ 50M. His technology leadership results in several leads for targets like ALF, PTP1B, SHP-2, DER, TNFR, Her-2, ZAP-70, IKKB, CD45, NY2R amongst others. He has had several successful grants from DARPA and SBIR. He has collaborated extensively with GSK, Novartis, J and J, DuPont, several Japanese, European and American companies in projects for lead discovery. Prior to Structural Bioinfofmatics, Inc., Dr. Ram was Head of Computational Chemistry at ImmunoPharmaceutics Inc., where he designed numerous drug leads, including highly specific endothelin-A receptor antagonists. This became Sitaxsentan, currently in Phase III clinical development by Encysive Pharmaceuticals. Dr. Ramnarayan holds a PhD in molecular biophysics from the Indian Institute of Science, Bangalore and has multiple papers and patents and several other patents pending. He is on the Advisory Board of the IBM BlueGene Initiative, Strand Genomics, Polyclone Bioservices and Keck Research Institute. He is on the Editorial Board of Current Proteomics.

His technology leadership results in several leads for targets like ALF, PTP1B, SHP-2, DER, TNFR, Her-2, ZAP-70, IKKB, CD45, NY2R amongst others.

Bin Xureceived his Ph.D. from Case Western Reserve University in 2004; and followed by postdoctoralstudies at Fred Hutchinson Cancer Research Center. Since 2011, he has been a tenure-track Assistant Professor in the Department of Biochemistry and Center for Drug Discovery at Virginia Tech. His research interests concern cell surface receptor-ligand binding, receptor signaling, novel ligand and receptor discovery, and translational structure-based and computer-aided ligand design with applications to novel peptide hormones and natural products relevant to diabetes, obesity,neurodegenerative diseases, and nanomedicine. He has published more than two dozens publications in premier international peer-reviewed journals.

His research interests concern cell surface receptor-ligand binding, receptor signaling, novel ligand and receptor discovery, and translational structure-based and computer-aided ligand design with applications to novel peptide hormones and natural products relevant to diabetes, obesity,neurodegenerative diseases, and nanomedicine

Tatsuya TAKAGI has completed his Ph.D. at the age of 32 from Osaka University.At that time, he had been an Assistant Professor of School of Pharmaceutical Sciences, Osaka University for 5 years. Then, since 1993, he had worked for the Genome Information Research Center, Osaka University as an Associate Professor until he became a professor of Graduate School of Pharmaceutical Sciences, Osaka University in 1998. He has published more than 100 papers in reputed journals and serving as Chairman of Division of Structure-Activity Relationship of the Pharmaceutical Society of Japan.

Genome Information Research

Dr. Prabagaran Narayanasamy is a faculty member in the Department of Pharmacology and Experimental Neurosciences at the University of Nebraska Medical Center. He received his PhD at IIT in Organic Chemistry and did his postdoctoral studies at North Dakota State University, Harvard University and University of Illinois Urbana-champaign. Later, he joined as a Research Scientist at Colorado State University to explore drug discovery. He has been a faculty at University of Nebraska Medical Center since 2012. Dr. Narayanasamy’s research interests are on development, delivering and discovering drug for anti-mycobacterial medicine and antiretroviral therapy. Conventional drugs and new inhibitors are used in nanoformulation to generate active nanomedicine. For antibacterial drug discovery - glyoxalase, quorum sensing, MEP and menaquinone pathway are utilized. Additionally, development of exosomes as drug delivering agent is initiated for infectious disease. In addition, metabolites are evaluated in the infected brain for characterizing neurodegenerative disorders.Biography

Development, delivering and discovering drug for anti-mycobacterial medicine and antiretroviral therapyResearch Interest

Andreia Valente completed her Ph.D. in 2010 from the Université de Lille I (France) on the field of Polymerization Catalysis. Then she joined the Organometallic Group at Faculty of Sciences,University of Lisbon (Portugal) where she got a first post-doc position in synthesis of organometallic compounds for nonlinear optic applications, followed by a second post-doc in the field of medicinal inorganic chemistry. Sheis presently a researcher (academic)at the same Institution, directing now her efforts to the synthesis of new polymer-metal complexes as targeteddrug-delivery systems in view to cancer therapy. To this ending, A. Valente counts with a multidisciplinary and enthusiastic team.

Medicinal Chemistry and Drug Delivery System

Bernhard Wünsch has completed his PhD in 1987 from the University of Munich. After postdoctoral studies at the University of Berlin, he finished his habilitation in 1993. Then he moved to the University of Freiburg and finally to the University of Münster, where he is director of the Institute of Pharmaceutical and Medicinal Chemistry. He has been the dean of the faculty from 2005-2006. He is member of the collaborative research center 656 (Molecular Cardiovascular Imaging) and the Cluster of Excellence CiM (Cells in Motion). He has published more than 200 papers in reputed journals

Originally the opioid receptor was subclassified into three subtypes, which were termed after their prototypical ligands μ (morphine), K (ketocyclazocine) and  receptors (SKF-10, 047). However, this hypothesis was disproved, since the pharmacological effects of typical σ receptor drugs were not reversed by the opioid receptor antagonists naloxone and naltrexone. Finally, σ receptors were recognized as specific, non-opioid, non-PCP, but haloperidol-sensitive binding sites consisting of σ1 and σ2 subtypes. The two σ receptor subtypes can be differentiated by molecular weight, tissue distribution, and ligand binding profile. It has been shown that the σ1 receptor plays an important role in several socially relevant human diseases including schizophrenia, depression, Alzheimer’s disease, and drug/alcohol addiction. Antagonists at the σ1 receptor potentiate the pain-relieving effects of opioid analgesics and, moreover, can be used for the treatment of neurogenic pain. Due to their over expression in several human tumor cell lines, σ1 and σ2 receptors are interesting targets for tumor therapy and diagnosis. In the lecture the interactions of ligands with the binding site of the σ1 receptor are analyzed. The design and synthesis of novel σ1 receptor ligands is presented. Spirocyclic piperidines and bridged piperazines represent very promising σ1 receptor ligands for further pharmacological evaluation. The development of a PET tracer for the imaging of σ1 receptors in the central nervous system is shown.

Mitsuji Yamashita was born in 1944 and has completed his PhD at the age of 27 years from Nagoya University, Japan, and postdoctoral studies from Toyota Science and Chemistry Research Institute, Japan, and Iowa State University, USA. He was a visiting professor of University of Massachusetts at Amherst, USA, and a researcher of Oxford University, UK, in 1994. He was promoted to be a professor of Graduate School of Science and Technology, Shizuoka University, Japan, in 1998 and retired at the age of 65 years old, and he is now a professor emeritus and specially-appointed professor of Shizuoka University, Japan. His research field is now focused on medicinal materials based on chemistry of carbohydrates and heterocycles. He has published more than 175 papers and patents as well as four books. Mitsuji Yamashita is now mainly concentrating in the research and development of phospha sugar antitumor agents and sugar dendritic Gd-DTPA MRI contrast agents for innovating in medical treatment for cancer patients.

By this research, novel multiple type low-molecular-weight antitumor agents of phospha sugar derivatives, which target IER5/Cdc25B and innovate in chemotheraputic treatment for cancer patients of various type of cancer cells, are developed. Sugar derivatives, whose oxygen atom in the hemiacetal ring is replaced by a nitrogen or a sulfur atom, etc., are called as pseudo sugars and well investigated. Among pseudo sugars phospha sugars in which the oxygen atom in the hemiacetal ring of sugars is replaced by a phosphorus moiety are not so well investigated in spite of important biological activities being expected for the pseudo sugar analogues. We have developed novel synthetic methodologies for preparing phospha sugar derivatives and constructed their compound library, and then preclinical evaluations have been carried out. Among the compound library of the phospha sugar derivatives, branched novel low-molecular-weight di- and tri-bromo deoxyphospha sugar derivatives (DBMPP and TBMPP) as well as some substituted phospha sugar analogues were found to exert novel, potential, and wide spectral antitumor activities by MTT in vitro evaluation method. The characterization and mechanism elucidation of these phospha sugar derivatives by flow cytometry and Western blotting showed that phospha sugars DBMPP and/or TBMPP enhanced the expression of cancer suppressors and suppressed the expression of cancer accelerators. Phospha sugar derivative TBMPP enhanced the expression of IER5 and then suppressed the expression of Cdc25B, which is the common and essential factor to act at the mitosis stage of the tumor cell cycles. Therefore, phospha sugar derivatives might induce apoptosis at G2/M stage and inhibit various kinds of cancer cells’ growth. In vivo evaluation for TBMPP against K562 cell transplanted to a nude mouse was checked visually to be successful. We are expecting that phospha sugars may be developed to be clinically useful novel antitumor agents.