Conference Day One: Monday, 14th September 2009
9:15 Registration and coffee
10:00 Chairman’s welcome & opening address
Dr. Peter Hamley
Director Parallel Synthesis
Sanofi-Aventis Deutschland GmbH, Germany
Enhancing the quality of the corporate compound collection
10:15 Approaches to chemical lead generation:
Is there a mystery of the East?
The economic downturn and apparent decreased productivity
of multinational pharmaceutical companies has resulted in major
shifts in the drug discovery landscape. The research facility closures
and job layoffs in the West have been counterbalanced by increased
investments in Asia, with India in particular emerging as a major
pharmaceutical player. A description will be given of the way in
which India’s top pharmaceutical company has shifted focus from a
purely generic mindset to one encompassing novel drug discovery.
Ranbaxy’s solution to finding novel chemical starting points will be
highlighted with examples selected from virtual and real chemical
libraries, natural product sources, and research collaborations.
Dr. Ian A. Cliffe
Director - Head, Medicinal Chemistry
Ranbaxy Laboratories Limited, India
10:55 External hit generation: library acquisition tailored to the needs
of early drug discovery projects
- Identification of favorable scaffolds / libraries
- Not Invented Here (NIH) / External innovation
- SAR acquisition and data mining
- Library and contract life cycle management
J&J is currently transitioning from traditional collection enhancement
to the more focused and tailored approach of External Hit
Generation. The presentation will outline how J&J uses Library Life
Cycle Management to 1) find the right balance between focus and
diversity in its compound acquisition, 2) capitalize on external
libraries to address direct needs from project teams and at the same
time enhance the corporate compound collection and thereby
3) guarantee benefits on the short as well as on the long term.
Peter Ten Holte
Associate Head of External Collaborations & Outsourcing Services
Johnson & Johnson Pharmaceutical Research & Development, Belgium
11:35 Coffee Break & Networking
Quality assurance for compound libraries and compound selection
12:05 Physical quality of Compound Libraries
Although physical characteristics such as compound purity and
solution concentration can be well defined, the concept of quality is
less tangible. Acceptable quality for one screening strategy may be
unacceptable for another. Flexible criteria for Quality Assurance
of diverse compound libraries take into account the intended
compound destinations, and some examples of this pragmatic
approach will be discussed.
Dr. Isabel Charles
Associate Principal Scientist
Global Compound Sciences, AstraZeneca UK Ltd., UK
12:50 Finding focus - selecting the best compounds for
acquisition and for HTS follow-up
The starting point for drug discovery programmes is often a
hit identified from high throughput screening (HTS), and the
subsequent rate of progress and chance of success is determined
by what hit is chosen and how it is subsequently modified.
In this talk factors that influence series tractability are outlined.
Furthermore, a means to use all the available information to find the
most interesting chemical series and to simultaneously guide
chemists’ attention to the parts of compounds to be retained and
away from those to be simplified is discussed.
With such principles it is shown one can also ensure that the right
compounds are selected for purchase or screening in the first place,
with due regard to ensuring sufficient novelty for patenting.
Schering Plough Ltd., UK
13:25 Networking luncheon
14:55 Compound library analysis at Bayer Schering Pharma
In 2006 Bayer acquired Schering ultimately leading to the unification of their screening compound libraries. The results of a thorough analysis of the combined Bayer Schering Pharma compound library will be presented in this talk. The following aspects will be addressed:
- Structural overlap between the two libraries and commercial libraries
- Assessment of library quality regarding identity, purity, stability and attrition
- Profile of the library with respect to physicochemical and ADMET properties
- Sources of HTS-hits that were progressed to lead and development compounds
In addition the technology platform for virtual screening of commercially
available compound libraries will be presented. The impact of this
technology in several projects is discussed.
Dr. Alexander Hillisch
Director, Medicinal Chemistry Lead Generation and Optimization – Medicinal Chemistry Wuppertal
Bayer Schering Pharma AG, Germany
Ideal library design for efficient lead finding
15:35 DNA Encoded Chemical Libraries
The isolation of specific binding molecules is a central problem in the
drug discovery process. While antibodies against virtually any given
target can nowadays be raised by biological display methodologies,
there is a clear need for the implementation of a similar “panning"
approach for the facile discovery of low- molecular weight binding
molecules. DNA-encoded chemical libraries represent a new tool
for the efficient identification of ligands to target proteins of choice.
Such libraries consist of a collection of organic molecules each
covalently coupled to a distinctive DNA tag that serves asamplifiable
identification bar code. We have applied different strategies for
the construction of large DNA encoded chemical libraries. In one
approach, termed ESAC (Encoded Self-Assembling Chemical library
technology), the combinatorial self-assembly of smaller sub-libraries
with distinct chemical groups at the 5’ and 3’ extremity of partially
complementary strands, yields large “dual-pharmacophore” libraries.
Alternatively, split-and-pool methods characterized by the introduction
of a DNA code after each synthetic step allow the construction of
large “single-pharmacophore” libraries. The implementation of next
generation high throughput sequencing now allows the fast and
efficient identification of binding molecules from DNA-encoded
libraries of unprecedented size.
Dr. Luca Mannocci
Institute of Pharmaceutical Sciences
Philochem AG, c/o ETH Zurich, Switzerland
16:15 Refreshment break
16:45 The optimisation of library hits to selective Alpha
2a antagonist tools
Over the last ten years, the Pfizer file has expanded from 500K
to > 3 million largely as a result of a directed File Enrichment
Initiative. Since then, we have found that the rapid optimisation of
biological activity is greatly accelerated when a series is amenable
to parallel synthesis. This presentation will discuss how we made
use of Alpha 2a HTS data and in silico PK models to design lead
optimisation libraries to deliver selective, CNS penetrant tools from 2
distinct chemical series.
- The presentation will provide an outline of the targeting of the Pfizer File Enrichment initiative
- How to make use of HTS data to direct hit optimisation library design
- Rapid lead optimisation was aided by use of in silico PK models
Research Fellow, Sandwich Laboratories
Pfizer Ltd., UK
17:25 Lessons learnt from target based drug discovery
Within the last 10 ten years we have experienced in animal health
drug discovery research that the target based approach implies
significant technical and intellectual challenge. Also in animal health
intensive efforts are necessary for new chemical entities in order to
obtain the best compound profile for biological activity and on target
activity. Especially in the field of anti-invectives and anti-parasitics we
need to address an effective knock out of the parasite and the
survival of the patient. Therefore it is essential to establish a good
starting point for candidate molecules and optimal processes in
order to accomplish all drug discovery tasks mentioned above.
In this talk we report about our approaches for a knowledge driven
compound selection and a compound vendor oriented process.
Dr. Joerg Cramer
Compound Logistics Manager
Intervet Innovation GmbH, Germany
18:05 Panel Discussion: Library building and screening modalities –
Which are the most promising concepts?
Discuss with our panelists which are the most effective and
efficient approaches in library design and how the choice of the right
screening modalities can optimise lead generation.
Dr. Peter Hamley
Director Parallel Synthesis
Sanofi-Aventis Deutschland GmbH, Germany
Panelists: Speakers of the day
Dr. Alexander Mayweg
Group Leader and Scientific Specialist
F. Hoffmann - La Roche Ltd., Switzerland
18:45 End of conference day one
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· [ Next: Conference Day Two: Tuesday, 15th September 2009 ]