The Laboratory Robotics Interest Group
Mid Atlantic Chapter
February 2010 Meeting
New Concepts and Approaches in Lead Discovery and
Optimization
Date: February 24, 2010
Place: Hyatt
Regency New Brunswick, 2 Albany Street, New Brunswick, NJ 08091
Phone: 732-873-1234, Fax: 732-867-2234
Itinerary: Dinner/Social Period - 5:00pm
to 7:00pm
Meeting & Presentations -
7:00pm
to 9:00pm
Registration:
http://lab-robotics.org/member/meetings.asp?rid=1
Agenda:
In drug discovery, time is money, and knowledge is
power. There have been three fundamental camps over the past two decades of
modern drug discovery, each championing three different keys required unlock
knowledge for drug receptor interactions. One camp holds that the key is to
better understand the space (occupancy) dimensions of D-R interactions with
improved modeling algorithms; another holds that a key is to understand the rate
(time) dimension of D-R interaction mechanisms. Both these approaches show
their power when diverse drugs leads are already in hand; therefore, the third
camp strives for approaches to accomplish lead finding through empirical drug
screening as efficiently and as validly as possible.
The Laboratory Robotics Interest Group, Mid Atlantic
Chapter presents four diplomats from these three camps to share their insight
on: “New Concepts and Approaches in Lead Discovery and Optimization”. We thank
Drs. Zhengming (Jimmy) Chen and Mel Reichman for organizing this session, and
especially thank the four acknowledged experts in their respective fields for
kindly accepting the invitations to speak.
Food and refreshments will be available FREE OF CHARGE
during the Dinner and Social Period.
Parking is also FREE OF CHARGE. On your way out of the parking
lot, just tell the attendant that you are with LRIG.
There is always a Job posting board at the social. Please encourage your recruiters to
give you material to post and distribute. Openings may also be posted at:
http://lab-robotics.org/forum/default.asp?CAT_ID=2.
There is no fee to attend the meeting.
Toward a kinetics-perceptive and MOA-informed paradigm for lead finding and
optimization
Rumin Zhang, Ph.D,
Senior Principal Scientist
Merck Research Laboratories, Kenilworth, NJ 07033
Abstract
An emerging paradigm of drug discovery lies in the
heightened appreciation for drug-target binding kinetics and mechanism of action
(MOA). This requires serious rethinking and retooling in the lead finding and
optimization phases of drug discovery so that only those kinetically fitting
compounds with the desired MOA will enter into development for a better chance
of success. This presentation outlines core critical issues contributing to
efficacy and safety and sketches a path toward a kinetics-perceptive and
MOA-informed approach of drug discovery.
Biography
Rumin Zhang is a
senior principal scientist in New Lead Discovery, Merck Research Laboratories,
Kenilworth, NJ. He obtained his Ph.D in biochemistry and biophysics from SUNY/Buffalo
in 1990 before joining Schering-Plough Research Institute. He has co-authored 35
peer-reviewed publications and is a co-inventor of 12 patents. An expert assay
designer, lead profiler and MOA detective, he advocates an emerging drug
discovery paradigm that is mechanistically savvy, kinetics-perceptive and
thermodynamics-informed.
A
leap forward in de novo ligand-receptor modeling
David L. Pompliano
PhD
Chief Executive Officer
Bioleap New Hope, PA 18938
Abstract
BioLeap is a
pre-clinical drug design company driven by proprietary, next-generation
computational fragment-based drug design (CFBDD) technology. Our platform
provides BioLeap's drug designers with the information and tools to rapidly
create new chemical entities, molecularly tailored to treat a particular disease
process. BioLeap changes the paradigm for identifying chemical starting points
and for deciding which compounds to make next during lead optimization,
obviating the need for costly high throughput screening (HTS) or synthetic
chemical tinkering. This is of particular value where conventional industry
approaches have been unsuccessful in progressing drug discovery efforts on
compelling targets.
Biography
Dr. Pompliano has
eighteen years of leadership experience in the pharmaceutical industry with a
focus on driving strategic change in research and development. Most recently he
served as Vice President, Worldwide Basic Head, Vaccines and Infectious Diseases
Franchise for Merck Research Laboratories. Prior to Merck, David was Vice
President, Head of Biology, Microbial Musculoskeletal and Proliferative Diseases
Center for Excellence in Drug Discovery at GlaxoSmithKline. Earlier in his
career, David served as Executive Director and Head of Antimicrobial and
Angiogenesis Research at DuPont Pharmaceuticals and as Director in the
Department of Biochemistry at Merck Research Laboratories. As a drug hunter,
David has contributed to the discovery or development of three marketed drugs (Tykerb,
Promacta and Altabax) and five drugs that have reached clinical proof of
concept. He is an internationally recognized scientist and innovator who has
published >50 research papers, has given >30 invited lectures internationally
and holds three patents for novel methods in drug discovery. Dr. Pompliano
received his B.S. (Chemistry) at the University of Virginia and his Ph.D.
(Chemistry) from Stanford University. David was a NIH Post-Doctoral Fellow at
Harvard University in the Department of Chemistry.
Acceleration
Exploration of Chemical and Biological Space with HTS
Mel Reichman, Ph.D.
Senior Investigator and Director
Lankenau Institute for Medical Research Chemical Genomics Center
Wynnewood, PA 19380
Abstract
We have implemented a
method of abbreviated high throughput screening (HTS) referred to as
orthogonal compression of compound libraries (OCL). When properly
applied, OCL can markedly reduce the resources required for successful HTS.
Enhancing HTS efficiency to discover novel drug leads more quickly and reliably
is important for smaller laboratories at biotechnology startups and throughout
academia. Measurable milestones will include: demonstrating significantly
improved positive confirmation rates, that false negative rates do not increase
and that the active pharmacophores in large compound libraries are more rapidly
discovered. We invite collaborators to participate.
Biography
Dr. Mel Reichman
received his Ph.D. in Neuroscience from the University of Rochester Center for
Brain Research Dr. Reichman has held several line-management leadership
positions in pharma. These include: Head, Cellular Pharmacology Laboratory at G.D. Searle; Head, Molecular Pharmacology Laboratory at Berlex Biosciences;
Director New Leads Discovery at Ligand Pharmaceuticals; Head, Head of Drug
Discovery Operations at Oncogene Science and Director, HTS Project Planning and
Management at DuPont Pharma. At each site, he has had a significant impact in
improving the efficiency and productivity of new leads discovery and in
progressing HTS hits to lead candidates.
Millsian 2.0: A
Molecular Modeling Software for Structures, Charge Distributions and Energetics
of Biomolecules
W. Xie, Ph.D.
Millsian, Inc.,
Cranbury, NJ 08512
Abstract
A
new molecular modeling software package, called Millsian 2.0, designed for
modeling the 3D structures, charge distribution and energetics of biomolecules
of pharmaceutical interests is available. Millsian software, built on a new
classical approach to solving atoms and molecules exploits analytical solutions
of molecular functional groups that it can superimpose to essentially
instantaneously render even large biomolecues such as proteins and DNA
fragments. The corresponding energy results are typically within 0.1% of
experimental values. Millsian’s build in 3D structure generation and
optimization facilities are able to create accurate 3D structures of molecules
from their 2D representation. It further calculates dipole moments and rotation
barrier heights for molecular conformation changes. The accurate electron
distribution in molecules makes Millsian an invaluable tool for pharmaceutical,
biotechnology, and chemical researchers to valuate molecules for binding sites,
reactive sites, and pockets.
Biography
Dr. Xie, Computational Chemist, graduated with a Ph.D. in Computational
Chemistry from the University of Minnesota, Minneapolis, MN. While in Minnesota,
Dr. Xie worked extensively on the development of the popular CHARMM biomolecular
modeling package. He has over 5 years of research experience in the developing
methodologies for the modeling of biological systems, algorithm design and
implementation. Dr. Xie is involved in developing the accurate molecular
modeling software based on classical physics principles for the prediction of
structure, energetics, charge distribution and other properties of molecules. He
has 7 peer-reviewed publications, 1 book chapter and been invited for conference
presentations on molecular modeling. He is also a reviewer of research papers
for Computational Physics Communications.
Menu
Crudities
Broccoli, Snow Peas, Celery and
Carrots,
Pumpkin Seeds. Olive and Roasted
Tomato
Tapenade, Spinach-Ranch, Sesame
Crackers and Wasa Crisps
INTERNATIONAL SLIDERS
Prepared in view
Maryland Crab Cakes with Micro
Greens and Pommery Remoulade
Australian Wagyu Beef
,Sharp Vermont White Cheddar, Caramelized Onions and Herb Mayonnaise
Thai Spiced Turkey
Cilantro and Cucumber with Hot and Sweet Chili Sauce
Mexican Pork
Chipotle and Salsa Verde
Served with Mini Brioche Rolls. Sugar Topped Biscuits, and Petite Cones of
Flavored Shoestring Fries
Desserts
Blackberry Fig Tarts
Tiramisu
Cannoli and Biscotti
Beverages
Assorted Sodas & Water
International Coffee &Teas
DON'T FORGET TO PRE-REGISTER TO INSURE THAT THERE IS ENOUGH FOOD AND SEATS.
http://lab-robotics.org/member/meetings.asp?rid=1
Visit The Laboratory Robotics
Interest Group homepage at http://lab-robotics.org
