 |
The Laboratory Robotics
Interest Group Mid Atlantic Chapter |
|
Celebrate the 125th Anniversary
|
|
Abstract Prior to 1992, the term 'HTS' in the published literature is almost nonexistent, although both targeted and untargeted 'mass' drug-screening programs were far from novel concepts by then. Most if not all the participants of this gathering would agree that pace and innovation in HTS technologies has revolutionized the drug discovery process. Yet, there is a kind of cloud over Pharma today, insofar as the perception that our drug pipelines ring more 'hollow' than they ought given the developments in biomolecular screening technologies over the past two decades. However, analysts on Wall Street not patients on 'Main Street' seed this notion. On the other hand, we recognize that technology alone cannot develop NMEs. The talk will provide an overview of some technological and historical milestones in modern HTS and relate these to the emerging importance of functional genomics and current discovery milieu in Pharma. |
2:00 Dr. Joe Loo
Group Leader, Pfizer Global Research and Development
"The Integration of Protein Mass Spectrometry into the Drug Discovery
Process"
|
Abstract Most biological targets for drug discovery are proteins. The recent advancement of mass spectrometry for the analysis of large proteins has impacted greatly the drug discovery process. In particular, biological mass spectrometry is an integral component of structural biology and emerging technologies such as proteomics. Structural data is used to improve the quality of target proteins employed in screening, structural studies driving drug design, and to elucidate mechanism of action, especially where post-translational modifications play a significant role. Sequence and purity determination and characterization of post-translational modifications of protein targets are key applications of MS. Assessment of protein folding and noncovalent drug binding by MS can be advantageous prior to more time-consuming high resolution structural studies by x-ray crystallography and NMR spectroscopy. Obtaining protein expression profiles by proteomics technologies has the potential to deliver insights to the mechanism-of-action of drugs and inhibitors. In addition, MS-based methods can potentially identify preclinical and clinical protein biomarkers to assess disease state, drug efficacy, and drug toxicity, greatly shortening the drug discovery and development timeline |
2:50 Break
3:20 Dr. R. A. Wildonger
Group Leader Automation and Laboratory Engineering, AstraZeneca
"Are Combinatorial Chemistry and Automation Providing What We Need In Drug
Discovery?"
|
Abstract:
Combinatorial and automated parallel methodologies have enabled the synthesis of vast numbers of small molecular entities as potential drug candidates. Indeed, these methodologies along with high throughput and even ultra-high throughput screening, in principle, have dramatically increased the likelihood of discovering and developing compounds suitable for commercialization. In this
presentation we will attempt to bring into focus some reasonable
expectations for deliverables from high throughput synthesis and attempt to
examine some of the more obvious pitfalls to avoid. We believe that
automation tools need to have a prominent place early in the exploratory
chemistry phase of a project and that a significant automation presence is
exercised through all synthetic phases of a project throughout its life. |
4:10 Dr. Manfred Auer
Executive Director of Innovative Assay Technologies, Novartis Research
Institute, Austria
"How to identify "drugable" targets?
CONA-BP-AIDA-Technology for screening orphan targets on the solid surface"
Abstract: Current concepts in miniaturized HTScreening technologies have to make optimal use of combinatorial chemistry and functional genomics. To effectively exploit compounds from split and mix combinatorial synthesis and the high number of new target proteins from functional genomics, Novartis and EvotecOAI developed the CONA-HTS (confocal nanoscanning - bead picking technology) as a novel high throughput - low hit-rate HTS process. In combination with the Novartis proprietary AIDA-Technology, quantitative on-bead confocal fluorescence screening can be combined with off-bead confirmation via a series of fluorescence techniques such as fluorescence intensity and anisotropy applied to equilibrium binding studies.
|
Lead Optimization
1:00 Introductory Remarks
1:10 Dr. Bruce Maryanoff
Distinguished Research Fellow, R.W. Johnson Pharmaceutical Research Institute
"Enhancement of Drug Discovery by Using Solid-Phase Organic Synthesis:
Optimization of Two Classes of Antithrombotic Agents"
|
Abstract
We have applied solid-phase organic synthesis (SPOS) in drug discovery research, especially to optimize antithrombotic lead compounds. (1) We rapidly improved a lead in our nipecotamide series of GPIIb/IIIa antagonists to arrive at RWJ-53308 (elarofiban), which advanced through Phase IIa clinical trials. The SPOS-based approach entailed the synthesis and evaluation of "mini-libraries", representing larger virtual libraries, in an evolutionary protocol. (2) A de novo design approach resulted in our indole-based, peptide-mimetic series of thrombin receptor (PAR-1) antagonists. Employing SPOS, we rapidly generated analogues and identified potent, selective PAR-1 antagonists, represented by RWJ-56110. Further optimization led to indazole RWJ-58259, which we used for in vivo proof-of-principle studies and for probing the physiological role of PAR-1. |
2:00 Dr. Christopher Cooper
Group Leader, Bristol-Myers Squibb Pharmaceutical Research Institute
"High Throughput Thematic Library Development and Production"
|
Abstract The dynamic environment of exploratory and early drug discovery across the pharmaceutical industry has necessitated important re-evaluations of the current paradigm at Bristol-Myers Squibb. Efforts to maximize the impact of high capacity combinatorial chemistry functions with high capacity biological screening have resulted in new strategic approaches to early drug discovery research. In concert with these approaches, Early Discovery Chemistry at BMS has developed a fully integrated suite of technologies to support the broad-based initiative of enhanced automated synthesis capability across the Institute. An overview of some of the newer devices and applications will be provided in this presentation. Finally, the recent introduction of the IRORI NanoKan Combinatorial Chemistry System platform to BMS's established workflow provides a new opportunity to: (i) increase library capacity and throughput, (ii) minimize variable production costs, and (iii) maintain rigorous product quality standards for solid-phase library analogues. Details from several recent NanoKan library syntheses will be presented |
2:50 Break
3:20 Richard Versace
Senior Scientist, Novartis Oncology
"Natural Products in Oncology Drug Discovery"
|
Abstract Complex natural products and their corresponding semisynthetic analogues have been utilized extensively as antitumor therapeutic agents. Paclitaxel and docetaxel are among the most successful examples. Although hundreds of natural products have been identified with antitumor properties, many will not be considered for development due to a poor therapeutic window, poor aqueous solubility, and/or the inability to produce the compound in large scale. There is clearly a need for natural product analogues that address these issues. Natural product total synthesis remains a key objective in synthetic organic/medicinal chemistry laboratories. However, there are relatively few examples where natural product total syntheses have been applied to the production of useful amounts of analogues with improved biological and physico-chemical properties. The efforts in this area by Novartis Oncology will be presented. |
4:10 Dr. Ron White
Senior Director, Drug Metabolism and Pharmacokinetics, Schering Plough
Research Institute
"Role of Drug Metabolism/LC-MS in Drug Discovery"
| Abstract In today's Drug Discovery process, Medicinal Chemistry, Therapeutic Area Pharmacology, and Drug Metabolism and Pharmacokinetics (DMPK) are equal partners in identifying chemical compounds with drug-like properties suitable for development as true drugs. LC-MS/MS now has assumed the role as the dominant analytical tool in DMPK support of Drug Discovery, especially in three areas: pharmacokinetics (PK), higher-throughput in vitro screening, and metabolite discovery and structural elucidation. In PK, LC-MS/MS allows the analytical chemist to rapidly develop sensitive assays that are almost guaranteed to be specific for the compounds to be tested. Surprisingly, this same property allows for relatively high-throughput in vitro DMPK screens, where the assay has to be specific for each compound tested, unlike usual high-throughput screens. Finally, powerful new MS hardware and software enable the DMPK scientist to find metabolites in the absence of a radiolabel and often determine an exact chemical structure |
4:00 - 7:00 PM
-Vendor Exhibits and Complimentary Buffet Dinner
-Student & YCC Poster Session
with prizes in various categories
Click
Here for Information on Presenting a Poster
-High School Student Mole Day Poster Contest Winners
7:00-8:00 PM Forum of Inventors & Awards
Dr. Edward J. J. Grabowski, Merck Process Research "Enantio and diastereo selectivity in the design of practical syntheses of pharmaceutically important compounds"
|
Abstract This is one of the most important current areas of synthetic organic research, and of fundamental importance to the pharmaceutical ndustry. Many drugs have handedness, and chiral methodology and syntheses are a very large part of what we do in the industry. Since I will be speaking at the session open to the General Public, I plan to begin with a small discussion of chirality, and where we see it in every day life ( i.e. right and left hands). Thereafter, I would show probably three uniqe solutions to synthetic problems relating to drugs in the AIDS, antibiotic and antidepressant categories, wherein we have been able to design practical syntheses of some reasonably complex drugs. |
Dr. Jack Johnston, Exxon-Mobil "Research and the Transportation Technology Revolution"
|
Abstract There is a revolution underway in transportation technology being driven by the twin forces of efficiency increase and emissions reduction. In the vanguard of this change are advances in sensing and measurement, computation, control theory, and mechanics all of which are supporting a much more fundamental investigation of the limits of internal combustion engine systems. Research designed to exploit the emergence of new capabilities needs to take into account the highly integrated nature of the chemical and physical processes at the heart of the engine system. An effective reasearch agenda requires well integrated team whose expertise encompasses physical, organic and analytical chemistry, chemical engineering, fluid dynamics and mechanics, computational theory, modeling, catalysis and materials science. The critical enabling science and technology for these systems has potential applications in other parts of the petrochemical industry as well. This talk will describe some of the changes being studied, the characteristics of such a research effort, and the opportunities for science in the transportation arena looking into the future.
|
Dr. Hendrik Schon, Lucent/Bell Labs "Plastic fantastic; electronic and optoelectronic devices based on organic materials"
Committee: Jeannette Brown, NJIT; Swapan Chowdhury, Schering-Plough; Alan Cooper, Schering-Plough; Fred Dammont, Jacqueline Erickson, Glaxo-SmithKline; Dennis France, Novartis; Robert Goodnow, Hoffmann LaRoche; Leonard Hargiss, Novartis; Mark Hayward, Novartis; Robert Larsen, Merck; Les McQuire, Novartis; Beth Miller, Rhom & Haas; John Penna, Governor Livingston High School; Ratna Shekhar, Novartis; Mal Sturchio, Indicator; Bill Suits, Chromatography Connections; Steve Waller, BMS; Andy Zaayenga, TekCel
|
EXHIBITORS |
| Amersham Pharmacia Biotech |
| Applied Biosystems |
| Argonaut Technologies |
| BD Biosciences Discovery Labware |
| Biacore |
| BIOPHILE |
| Bio-Tek Instruments |
| BioWhittaker |
| Chemo Dynamics |
| Corning |
| CyBio |
| Genevac |
| Gilson |
| Glas-Col |
| Greiner BioOne |
| Groton NeoChem |
| Hudson Control Group |
| IDBS |
| IGEN International |
| Labman Automation |
| Labvantage |
| LEAP Technologies |
| Matrix Technologies |
| MetaChem / ANSYS |
| Micromass |
| Millipore |
| MWG Biotech |
| Nalge Nunc |
| Nichiryo America |
| NuGenesis |
| Orochem |
| Packard BioScience |
| PerkinElmer Life Sciences |
| Personal Chemistry |
| Phenix Research Products |
| Query+ |
| Remp |
| Sparton Medical Solutions |
| Thermo Finnigan |
| TimTec |
| Titertek Instruments |
| TOMTEC |
| Waters Corporation |
| Zymark |
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Directions:
The college web site:
http://www.middlesex.cc.nj.us/
Maps & Directions:
http://www.middlesex.cc.nj.us/admin/mpi/mapdirs/campusmap.htm
The meeting will be held at: CC College Center
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Reserve the date. For further details, directions, and registration see the
web site (http://www.njacs.org/acs125.html), or September-October Indicator.
Due to limited seating and the anticipated number of attendees, we must limit
the number of free registrants on a first come first serve basis.
Pre-registration is required (deadline: November 1). ONLINE REGISTRATION
PREFERRED at (http://www.njacs.org/acs125.html). Use the form below for registration, if you
cannot register online.
--------------------------------------------------------------------------------
Name: ________________________________________
Affiliation:_____________________________________
Address:______________________________________________________________________
Telephone:___________________FAX:_______________________Email:__________________
Please check the following: Attending: Drug Discovery Symposia- Lead
Discovery___, or Lead Optimization___
4PM events____, Panel of Inventors & Awards____
Please return to: Dr. Robert Goodnow, Jr., Hoffmann-La Roche, 340 Kingsland
Street, Nutley, NJ 07110-1199
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Exhibitor
information at:
https://www.lab-robotics.org/Mid_Atlantic/meetings/0111_exhibit_information.htm
|
|
