Conference Day One: Monday, 14th September 2009

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

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. Brad Sherborne Head CMC Schering Plough Ltd., UK

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

16:45 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

Andy Bell
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.

Chairman:

Dr. Peter Hamley
Director Parallel Synthesis
Sanofi-Aventis Deutschland GmbH, Germany

Panelists: Speakers of the day

Guest Panelist:

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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