5^th International Conference on Medicinal Chemistry & Computer Aided Drug Designing and Drug Delivery December 05-07, 2016 Phoenix, Arizona, USA

Dr. L. Mario Amzel is a director and professor in school of medicine of The John Hopkins University. He completed his PhD from Universidad de Buenos Aires, Argentina during 1968.

Structural Mechanistic Biochemistry. Enzymes play a key role in all metabolic and cell-signaling processes. Characterization of an enzyme’s biological function must include the description of its mechanisms at an atomic level. Our laboratory is deciphering the catalytic mechanism of several enzyme families, using a combination of molecular biology, biochemistry and structural Biology. Systems under study fall into two classes: 1) Enzymes that recognize or process phosphates and 2) redox enzymes. These systems include: ATP-synthase, pyrophosphate hydrolases, farnesyl pyrophosphate synthases, PI3K, flavoenzymes, copper hydroxylases, and non-heme iron oxygenases. All experiments necessary to address mechanistic questions are carried out in the laboratory. Cloning and expression, ultrapurification, kinetic characterization, mutational analysis, mass spectrometry, crystallization, and structure determination by x-ray diffraction are some of the techniques we bring to bear to characterize the mechanisms of these enzymes. In addition to being intrinsically interesting some of these systems are being developed as targets for drug design. Structural Thermodynamics. Most biological processes rely upon recognition and binding among macromolecules. We have developed several systems, such as anti-peptide antibodies and lectins, that we are using to study protein-ligand interactions. As part of this research, we are developing computational methods to calculate the changes in the thermodynamic variables (ΔG, ΔH, ΔS) that take place when a protein recognized another macromolecule or a small ligand. Techniques used in this work involve monoclonal antibody development, x-ray diffraction and calorimetry, followed by empirical parameterization, and molecular mechanics/dynamics and statistical mechanics calculations. Results of these studies have a major impact on our understanding of binding energetics, including the estimation of binding affinities for structure-based drug design.

Degree in Chemistry, Cambrige University, England, 2012 CEO of Thistlesoft Recent Publications: 1.McMartin C. A geometry force field which converts low-resolution X-ray models to structures with properties found at ultra high resolution Protein Sci., 2012 ,21(1), 75. 2.McMartin C, Bohacek RS. QXP: powerful, rapid computer algorithms for structure-based drug design. J Comput Aided Mol Des. 1997 Jul;11(4):333-44. with properties found at ultra high resolution Protein Sci., 2012 ,21(1), 75.

His reserch interest includes A geometry force field which converts low-resolution X-ray models to structures with properties found at ultra high resolution Protein and QXP: powerful, rapid computer algorithms for structure-based drug design.

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).

In addition to lecturing and laboratory teaching during 25 years at the University of Arizona, and the publication of more than 125 scientific papers, he has mentored a large number of undergraduate, graduate (16 Ph.D.s granted, 3 in progress) and post-doctoral students who have taken positions in academia, industry and the US government. His Ph.D.s have hailed from the US (9), Czech Republic*, China, India, Iran*, Ireland, Kenya*, Korea, Mexico* and Sri Lanka. Four of these Ph.D. students (*) have gone on to become naturalized citizens or permanent resident status. Recent undergraduates associated with his research group have gone to graduate schools at Harvard, MIT, Boston University, University of Wisconsin, and Columbia University.

Dr. Polt began his research career by developing methods for amino acid synthesis in Prof. Marty O’Donnell’s lab at IUPUI. After that he was trained in the art of Organic Synthesis in the laboratories of Profs. Gilbert J. Stork at Columbia University and Dieter Seebach at the ETH in Zürich. He has continued to develop novel synthetic methods for amino acids, amino alcohols, glycosides and glycopeptides. Application of these methods has resulted in the production of a number of pharmacologically active glycopeptides, alkaloid-like inhibitors of glycolipid processing enzymes and glycosyltransferases, as well as glycolipids with biological activity such as glycosphingolipids and rhamnolipids. He discovered a new class of glycosphingolipids in the insect Manduca sexta— biologically active sphingomyelins and glycosides derived from dienylsphingosine, and has developed methods for their synthesis, as well as the synthesis of rhamnolipids from Pseudomonas aeruginosa. The biological focus of his work has been in attempting to understand the chemistry of carbohydrates (e.g. glycolipids, glycoproteins) at cell membranes, membrane trafficking, and using these insights to design glycopeptide drugs from peptide neurotransmitter (neuromodulators, hormones) with enhanced stability in vivo that are capable of penetrating the Blood-Brain Barrier and interacting with GPCRs as agonists or antagonists. Clinical applications include pain, migraine, Parkinsons, Alzheimers and other neurogenerative diseases. In addition to lecturing and laboratory teaching during 25 years at the University of Arizona, and the publication of more than 125 scientific papers, he has mentored a large number of undergraduate, graduate (16 Ph.D.s granted, 3 in progress) and post-doctoral students who have taken positions in academia, industry and the US government. His Ph.D.s have hailed from the US (9), Czech Republic*, China, India, Iran*, Ireland, Kenya*, Korea, Mexico* and Sri Lanka. Four of these Ph.D. students (*) have gone on to become naturalized citizens or permanent resident status. Recent undergraduates associated with his research group have gone to graduate schools at Harvard, MIT, Boston University, University of Wisconsin, and Columbia University.

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.

Professor Hulme has extensive experience of each phase of the drug discovery value chain having had functional responsibility for > 55 individual targets over a 20 year period and built two compound collections spanning both private and public sectors. He obtained his PhD at age 25 under the tutelage of Professor Jack Baldwin at Oxford University. He moved to the University of Arizona in 2007, after holding senior management positions at Sanofi-Aventis (’94-’99), Amgen (’99-2004) and Eli Lilly (2004-2007) establishing and running High-throughput Medicinal Chemistry groups. In 2010, he was the founder of BIO5 Drug Discovery after being the recipient of a $7.5 million grant from the NIH. In 2011, he was named the University of Arizona Innovator of the Year. He has over 185 papers, patents, abstracts and book chapters to his name with current research interests including targets for Alzheimer’s, prostate and colon cancer, and multi-component reaction/methodology development for file enhancement.

His research interest includes targets for Alzheimer’s, prostate and colon cancer, and multi-component reaction/methodology development for file enhancement

Prof. Tepe recieved his PhD from the University of Virginia in 1998 with Prof. T.L. Macdonald and completed his post-doctoral studies with Prof. R.M. Williams at Colorado State University in 2000. Research in his lab is primarily focused on the synthesis and use of natural products and their analogues to interrogate proteasome-mediated signaling pathways. Using the new synthetic methods, drug-like derivatives of natural products are prepared and interrogated for their clinical significance in vitro, cell culture and animal models. For his academic drug discovery efforts aimed at multiple myeloma, he received the American Cancer Research Scholar award, Senior Award from the Multiple Myeloma Research Foundation in 2008, and Multiple Myeloma senior award in 2010, and the International Myeloma Senior Award in 2013.

His research program provides an interdisciplinary blend of synthetic and medicinal chemistry that includes the total synthesis of natural products, the discovery of new reactions, as well as the evaluation for their cellular mechanism and medicinal properties. Natural products are still the primary source for medicines, and marine sponge metabolites represent a highly diverse and complex class of natural products with remarkable biological activities. Our laboratory is focused on the total synthesis of marine sponge alkaloids, to examine their potent anti-cancer and anti-neurodegenerative properties.

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.

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

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.

Marc Le Borgne has completed his PhD at the age of 31 years from Nantes Atlantic University after Pharmacy studies (6 years). He is the director of EA 4446 B2MC, a research group dedicated to Drug Design, Synthesis and Structural Optimization. He has published more than 60 papers in reputed journals and is serving as an editorial board member of Pharmaceuticals (since 2016). He gave some invited lectures abroad (Saarbrück, Duesseldorf, Oslo, Tromsø, Bergen, Debrecen, Sacramento, Helsinki, Oulu...). He is developing bioactive small molecules targeting kinases, efflux pumps and CYPs

Design, synthesis and structural optimization of functionalized small molecules as anticancer agents (CK2, Dyrks), efflux pump inhibitors (Pg-p, BCRP) and anti-infective agents (CYP51, vaccines). Some scaffolds developed: indole, naphthyridine, indeno[1,2-b]indole, steroids, peptidomimetics, polysialic acid.

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

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.

Marjana Novič has completed her Ph. D. in Chemistry from University of Ljubljana. Currently she is a associate professor in National Institute of Chemistry

Her research interest includes Hierarchical Clustering and Recognition of Chemical Structures and Structural Fragments on the Basis of 13C NMR spectra.

Nicolas Moitessier is an Associate Professor at McGill University, Montréal, Canada. He received his undergraduate training and his Ph.D from Université Henri Poincaré-Nancy I (France) under the guidance of Dr. Yves Chapleur within the Groupe SUCRES. He carried out thesis research on computer-aided design and synthesis of carbohydrate-based biologically relevant molecules. He was first involved in the design and preparation of IP3 and Adenophostin A mimics using Sharpless asymmetric dihydroxylation as a key reaction. In collaboration with a theoretical chemistry group (headed by Dr. Maigret), he then focused on the computer-aided design and synthesis of carbohydrate-based antagonists of integrins. In 1998, he moved to Montréal where he joined Prof. Stephen Hanessian group. His interests involved the docking study and the asymmetric synthesis of conformationally constrained MMP inhibitors. He was also involved in a project related to the preparation of aminoglycosides as antibiotics and in the design and preparation of BACE-1 inhibitors. In 2001, he moved back to Nancy to start an academic career (Chargé de Recherche, CNRS) then back to Montréal in 2003 (Assistant Professor, McGill University). In 2009, He was promoted to Associate Professor. His current research interests integrate computational chemistry and organic/medicinal chemistry, spanning from software development to sugar chemistry and synthetic methodology. Among his achievements are the development of directing-protecting groups for regioselective carbohydrate functionalization, the development of a fully integrated computer-aided drug design platform (Forecaster) and computational catalyst/biocatalyst platform (Virtual Chemist), the development of novel methodologies for the synthesis of chiral cyclic and bicyclic scaffolds, the design, synthesis and evaluation of potential drugs with a focus on Alzheimer's disease and cancer. Current computational efforts include the development of a novel molecular mechanics method, the development of tools for reactive metabolite predictions, for drug-drug interaction and covalent drug binding. In the wet lab, students and post doctoral fellows are developing asymmetric catalysts, biocatalysts, anti-cancer therapeutics and transient directing protecting groups. In 2008, he received the first Reginald Fessenden Professorship in innovation for the development of the Forecaster platform in drug discovery. In 2009, he was awarded the AstraZeneca Award in Chemistry. In 2010, he co-founded Molecular Forecaster, a company distributing the developed software and providing service and consulting to local and international pharmaceutical and biotechnology companies. Nicolas is co-author of 70 publications, 2 registered copyrights, and co-inventor of 2 patents and 4 reports of invention.

Chemistry and Drug Designing

Pierre Falson got his PhD at the LYON University. He is a CNRS (National Centre for Scientific Research) Research Director, enzymologist and membrane proteins biochemist, co-leading the Drug resistance mechanism and modulation team in the BMSSI CNRS-UCBL1 Research Unit. PFhas published 54 publications, patented 6 inventions and licensed2 to CALIXAR, a startup which he co-founded. He was awarded in 1991 by the Maurice Nicloux prize from the French Society of Biochemistry and Molecular Biology, in 2010 and 2011 by the “National competition of innovative start-ups” and by the Innovation and Transfer Technology prize from theCNRS.

The “Drug Resistance Mechanism and Modulation” group is studying the molecular and cellular mechanism of multidrug ABC (“ATP-binding cassette”) transporters which are responsible for cellular resistance to multiple chemotherapeutics.

Dr. Alexander Heifetz is a Principal Scientist at Evotec (UK) Ltd, a drug discovery services company. He provides CADD expert support for drug discovery programs. He obtained his PhD from the Weizmann Institute of Science, Israel, in 2001 under supervision of former Israeli president and Foreign Member of the Royal Society, Prof. Ephraim Katzir and Dr. Miriam Eisenstein. Dr. Heifetz has more than 12 years of experience in drug discovery industry (EPIX Pharmaceuticals and Evotec) and was involved in discovery of 3 clinical drug candidates for treatment of anxiety, major depressive disorder, pulmonary hypertension, and Alzheimer’s disease. He has more than 18 patents, patent applications and a wide range of publications in the area of medicinal chemistry and molecular modelling. Recently, he received the Royal Society Industry Award and established a collaboration with academic group of Dr. Phillip Biggin from the University of Oxford, for development of methods for GPCR modelling.

Medicinal chemistry, molecular modeling, drug discovery

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.

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

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