HUM-MOLGEN events: Drug Design & Medicinal Chemistry Conference

Day 1 - Thursday, May 8, 2014

7:00

Check In & Registration

8:00

Welcome & Opening Remarks

Rising Targets: Epigenetics

8:05

KEYNOTE PRESENTATION

TBA

8:45

Speaker TBA, Epizyme

9:10

Targeting Protein Methyltransferases at the SGC: Screening Libraries, Protein Structures and Chemical Probes

Matthieu Shapira, Associate Professor, University of Toronto

9:35

Stefan Knapp, Professor, University of Oxford

10:00

Morning Networking & Coffee Break

Rising Targets: Protein-Protein Interactions

10:30

Olivier Sperandio, Drug Designer, Protein-Protein Interactions, INSERM France

10:55

Computationally Guided Discovery and Development of non-LBP Novel Androgen Receptor Small Molecule Antagonists - Improving Treatment of Prostate Cancer

Darren Fayne, Senior Research Fellow, Trinity College Dublin

Prolonged treatment of prostate cancer (PCa) leads to developed resistance so alternative therapies are urgently required. By developing compounds which interact with the androgen receptor (AR) distant from the endogenous dihydrotestosterone binding site and block co-activator recruitment it is possible to overcome this resistance regardless of the AR mutation status. Three recently published papers [PMID: 22280402, 22853713 and 23834240] detailing our compounds demonstrate non-ligand binding pocket (LBP) AR affinity, selectivity over other nuclear receptors and low toxicity, point to the viability of an alternative approach to classical PCa therapy.
My talk will detail the computational screening and design approaches applied, discuss SAR around the lead series and give an overview of the biological assay data.

11:20

Christian Ottmann, Associate Professor, Biomedical Engineering, Technische Universiteit Eindhoven

11:45

Lunch on Your Own

Rising Targets in the Ubiquitin System

1:15

Ingrid Wertz, Scientist and Project Team Leader, Department of Early Discovery Biochemistry, Genentech

1:40

Stig Linder, Professor, Experimental Oncology, Vice Chairman, Oncology and Pathology, Karolinska Institute; Adjunct Professor, Molecular Oncology, Medical Sciences, Uppsala University

2:05

Anjanabha Saha, Senior Scientist, Proteostasis Therapeutics Inc.,

2:30

PANEL DISCUSSION: Establishing Academic Drug Discovery Centers

3:15

Afternoon Networking & Coffee Break

New Drug Delivery Systems

3:45

Paul Polakis, Director, Staff Scientist, Discovery Oncology, Genentech

4:10

Éric Marsault, Professor, Pharmacology, Université de Sherbrooke

4:35

Daniel Obrecht, Co-Founder & Chief Scientific Officer, Polyphor

5:00

Antimo Gioiello, Assistant Professor, Pharmaceutical Sciences, University of Perugia

5:25

Oral Presentations from Exemplary Submitted Abstracts

To be considered for an oral presentation, please submit an abstract here by April 8, 2014. Selected presentations will be based on quality of abstract and availability. Presentation slots fill up fast so please submit your abstract ASAP.

6:00

Evening Networking Reception

Day 1

Day 2

Day 2 - Friday, May 9, 2014

8:00

Opening Remarks

Modern Technologies in Medicinal Chemistry

8:05

Thomas Franch, Chief Scientific Officer, Nuevolution A/S

8:30

Halogen Bonding – Principles and Applications in Drug Discovery

Frank Boeckler, Professor, Medicinal Chemistry & Drug Design, Eberhard Karls Universität Tübingen

Molecular interactions embody the dialog between chemistry and biology. A thorough understanding of the applicability and limitations of molecular interactions is the basis for success and innovation in drug discovery. Halogen bonding has recently experienced a renaissance, gaining increased recognition as an important and useful molecular interaction in the life sciences. Halogen bonds are favorable, fairly directional interactions between an electropositive region on the halogen, the ?-hole, and a number of different nucleophilic binding partners. I will illustrate the nature, strength, tunability, and preferred geometry of halogen bonds and highlight, how insights gained by first principle calculations can be transformed into molecular design strategies and algorithms. A new experimental approach for studying halogen bonds is the concept of halogen-enriched fragment libraries (HEFLibs). These libraries consist of unique chemical probes of low molecular complexity and high diversity. They facilitate the identification of favorable halogen bonds by sharing the advantages of classical fragment-based screening. Besides providing insights into the nature and applicability of halogen bonding, the use of HEFLibs also provides smart starting points for hit-to-lead evolution.

8:55

Jesús Alcázar, Senior Scientist, Janssen

9:20

Gisbert Schneider, Professor, Institute of Pharmaceutical Sciences, ETH Zürich

9:45

Helena Danielson, Professor of Biochemistry, Uppsala University

10:10

Morning Networking & Coffee Break

Novel Computational Methods

10:45

Data-Driven Medicinal Chemistry in the Era of Big-Data

Scott Lusher, Director, Applied eScience, Netherlands eScience Center

Science, and the way we undertake research is changing. The current scale of data-generation is providing incredible opportunities for data-driven research, with the potential to transform our current practices. The exploitation of so-called “Big-data” will allow us to undertake research projects never previously possible, but should also stimulate a re-evaluation of all our data practices. Data-driven medicinal chemistry approaches have the potential to improve decision making in drug discovery projects provided all researchers embrace the role of data-scientist and uncover the meaningful relationships and patterns in available data. This represents the latest evolution of medicinal chemistry.

• Medicinal chemistry, like other scientific disciplines, is the subject of increased data generation which provides new opportunities for innovation and discovery.
• Combinations of technical developments and behavioural changes are required for medicinal chemists to exploit the potential benefits of the big-data era.
• Successful medicinal chemists will increasingly be those that further embrace the role of data-scientist.
• All scientific disciplines, including medicinal chemistry, are the subject of a revolution as data is generated at unprecedented rates and its analysis and exploitation become increasingly fundamental to innovation.

11:10

Gerhard Ecker, Professor, Medicinal Chemistry, University of Vienna

11:35

Gisbert Schneider, Professor, Institute of Pharmaceutical Sciences, ETH Zürich

12:00

Lunch Provided by GTC

1:15

Using Bioactivity Databases and Computer Algorithms for Target Deconvolution and Compound Design

Andreas Bender, Lecturer for Molecular Informatics and Drug Design, University of Cambridge

More and more chemical and biological information is becoming available, both in public databases as well as in company repositories. However, how to make use of this information in chemical biology and drug discovery settings is much less clear. In this work, we will discuss how chemical and biological information from different domains – such as compound bioactivity data, pathway annotations from the bioinformatics domain, and gene expression data – can be used for a variety of purposes, such as the mode-of-action analysis from phenotypic readouts, anticipating compound toxicities in early discovery, and for designing and selecting compound with the desired bioactivities. We will show that cheminformatics algorithms trained on large chemogenomics databases can be employed to support target deconvolution in high-content screening as well as organism-based screens using e.g. Xenopus laevis as well as phenotypic data obtained from rat models. When anticipating compound adverse compound properties early on, we will show than gene expression data can be used for this purpose; however, how to generate and analyze data is very much case-dependent. Relating to compound design and selection, we can employ both bioactivity-driven approaches as well as gene expression based resources, and examples of both will be presented. Hence, overall, while the chemical and biological data available currently is very diverse, we are able to show that it can already be used successfully for understanding the mode of action of compounds, anticipating their toxicities early on in discovery, and designing and selecting novel chemical matter to modulate biology.

1:40

Anna Vulpetti, Senior Investigator, Novartis

2:05

Antibody Drug Conjugates as Cancer Therapeutics

Paula Petrone, Scientist, Roche

Appending highly potent cytotoxic compounds to antibodies enables the specific delivery of chemotherapeutics to tumor cells. Recent advances in antibody drug conjugate (ADC) technology including linker chemistry, new payloads and site directed conjugation will be discussed along with early clinical results for selected ADCs.

2:30

Novel Computational Tools for Discovering Compounds for Difficult Targets

Alexander Dömling, Professor, Drug Design, University of Groningen

2:55

Closing Remarks & Conference Concludes