In silico ADMET
Provider: Faculty of Health and Medical Sciences

Activity no.: 3118-15-00-00 
Enrollment deadline: 01/08/2015
Date and time14.09.2015, at: 09:00 - 18.09.2015, at: 16:00
Regular seats15
Course fee6,120.00 kr.
LecturersLars Olsen
ECTS credits4.50
Contact personMarianne Wieslander Jørgensen    E-mail address: marianne.joergensen@sund.ku.dk
Enrolment Handling/Course OrganiserPhD administration     E-mail address: phdkursus@sund.ku.dk

Aim and content
Learning objectives
The course objectives are to introduce participants to different in silico methods for prediction of ADMET (absorption, distribution, metabolism, excretion, and toxicology) endpoints. The application of in silico methods in the study of relationships between molecular structure and ADMET properties are dealt with in detail. The course will provide the participants with hands-on experiences and the opportunity to apply in silico methods to their own research problems.

Content
Bioavailability is an important issue in the drug discovery and development process. The bioavailability of a compound is a complex property depending on solubility, absorption, permeability, metabolism and excretion. Furthermore, the toxicity of a compound, eventually its metabolites, is also important for a compound in relation to its use as a drug. In studies of drugs and potential drug compounds, it has become more and more important at an early stage to consider, if compounds has drug-like properties. Thus, there is a tendency not only to optimize potency, selectivity etc., but simultaneously optimize the ADMET profile of the compounds.

The course is aimed at researchers including PhD students, who work with biologically active molecules, and who would like to be able simultaneously to consider the ADMET properties of the compounds. The course is also relevant for people involved in regulatory aspects of drugs.
The course will focus on the following five themes:
1) Introduction to ADMET properties and in silico methods. Here the participants will learn the SMILES notation used for describing chemical structures, and perform structural queries on web-based databases and servers.
2) Prediction and use of ADMET properties in drug discovery and development.Here the participants will learn about data and model quality, QSAR methods, and perform structure optimization and compound profiling using the StarDrop program and StarDrop plug-ins from Optibrium Ltd., UK (http://www.optibrium.com).
3) Prediction of toxicity. Here the participants will learn about expert systems and use the Derek Nexus and Sarah Nexus expert systems from Lhasa Ltd., UK (http://www.lhasalimited.org) to predict toxicologic end-points like mutagenicity, genotoxicity and hepatotoxicity.
4) Prediction of metabolism and site of metabolism. Here the participants will explore CYP450 3D structure, learn about the enzymatic reactions forming metabolites, classify CYP450 isoform specificity and predict site of metabolism using the SMARTCyp and WhichCyp programs developed by the course organizer.
5) Population-based pharmacokinetic modelling and simulation. Here the participants will learn to create a virtual population of patients and simulate their pharmacokinetics using the Simcyp Simulator from Simcyp Ltd., UK (http://www.simcyp.com).


The practical exercises will include tutorials and hands-on work aimed at learning to apply the above programs on the participants’ own research activities.

During the course the participants will be exposed to a variety of in silico methods ranging from simple statistical methods via advanced molecular simulation methods to expert systems. The theoretical basis for the methods will be covered from an application point-of-view.

Participants
The course addresses PhD students with an MSc degree in biochemistry, biology, chemistry, pharmacology or pharmacy, or research scientists in the pharmaceutical industry.

Language
English

Form
The course will be organised as a one-week course and will comprise 20 lectures and approx. 20 hours' practical exercises and discussions. Lecture notes and selected scientific publications will be used. During the course the participants should prepare a Powerpoint presentation with their results as documentation for active participation in the course.

Course director
Associate Professor Lars Olsen and Professor Flemming Steen Jørgensen, Department of Drug Design and Pharmacology at the Faculty of Health and Medical Sciences, University of Copenhagen.

Teachers
Associate Professor Lars Olsen and Professor Flemming Steen Jørgensen, Department of Drug Design and Pharmacology and Associate Professor Bente Steffansen, Department of Pharmacy at the Faculty of Health and Medical Sciences, University of Copenhagen and external lecturers from industry.

Course secretary
Marianne W. Jørgensen (e-mail: marianne.joergensen@sund.ku.dk)

Dates
14. - 18. September 2015

Course location
Lectures and practical exercises will take place in the Benzon Auditorium, Universitetsparken 2.