OVERVIEW

The course is aimed at third-year students of the Single-Cycle master’s degree in pharmacy and provides 6 training credits corresponding to 48 hours of classroom teaching. It allows the student to learn and discuss the main strategies for designing a drug and for performing its experimental validation, focusing in particular on the elucidation of the mechanism of action at the molecular level, i.e. the molecular interaction between the potential drug and the biological macromolecule.

At the end of the course, the student knows various computational and experimental pharmacology methodologies applied in drug discovery and knows how to apply them in the correct context. He is also able to design the experiments  to investigate the action of a drug of interest on living organisms, through in-vitro and in-vivo methods.

AIMS AND CONTENT

LEARNING OUTCOMES

The course aims to illustrate and discuss the main strategies for drug design and its experimental validation, with particular focus on elucidating the mechanism of action at the molecular level, namely the molecular interaction between the potential drug and the biological macromolecule. It also

addresses the preclinical validation of the compound under investigation, with the goal of laying the foundations for clinical trials and the eventual marketing of the new drug.

AIMS AND LEARNING OUTCOMES

Obiettivi e apprendimento

The educational objective of the course is to provide students with the basic competencies related to the process of drug design and experimental validation. In particular, students will become familiar with various types of design strategies and experimental testing approaches and will be able to apply them in the appropriate context.

At the end of the course, students will be able to:

· Describe computational and experimental pharmacology methodologies applied in drug discovery.

· Apply these methodologies in the appropriate context.

· Design a preclinical study for a drug of interest by combining in vitro, ex vivo, and in vivo approaches to assess its efficacy and potential toxicity.

· Present and describe such a design using appropriate scientific language.

PREREQUISITES

Knowledge of basic notions of pharmaceutical chemistry, biochemistry, organic chemistry,pharmacology and toxicology, animal biology.

TEACHING METHODS

The course is organized in frontal lessons. The topics will be illustrated by the teachers through Powerpoint presentations that are shared on the module TEAM.

Any Student with documented Specific Learning Disorders (SLD), or with any special needs, shall reach out to the Lecturer(s) and to the dedicated SLD Representative in the Department ( Prof. Luca Raiteri, Luca.Raiteri@unige.it ) before class begins, in order to liaise and arrange the specific learning methods and ensure proper achievement of the learning aims and outcomes. VERY IMPORTANT: any request for compensatory tools and adaptations in the exam MUST be done within 7 working days before the date of the exam according to the instructions that can be found at https://unige.it/disabilita-dsa/comunicazioni

SYLLABUS/CONTENT

Drug design: Ligand-based drug design, ligand 3D representation, force fields, conformational analysis, energy minimization, Ramachandran plots, pharmacophoric maps, molecular descriptors, basis of QSAR e 3D-QSAR. Structure-based drug design, docking and molecular dyamics, baisis of homology modelling. Virtual screening, drug repositioning. Databases in drug discovery, drug design project workflows.

Experimental Pharmacology: introduction to experimental pharmacology as an experimental approach for the qualitative and quantitative evaluation of the action of a newly formulated drug (experimental design with application of in vitro, ex vivo, and in vivo methodologies and techniques); illustration of the preclinical development pathway of a drug prior to its market release; use of immortalized cell lines, primary cultures, and iPSCs for in vitro studies; application of the main functional assays and molecular techniques to define the effect of the drug under investigation (e.g., cell viability and metabolism tests, study of gene modulation and protein expression of biological targets potentially affected by the drug) using 2D in vitro models; overview of the main advantages and limitations of 2D in vitro models and introduction to new 3D in vitro models with or without scaffolds (spheroids, organoids, organ-on-chip, and 3D bioprinting systems); description and use of the main ex vivo methodologies for preclinical drug studies (acute slices, organotypic slices, isolated and perfused organs) and the experimental analyses applicable to them; legislation and ethical regulations governing the use of animals in research and preclinical studies; selection of the most appropriate animal model; description of the main animal models of disease (spontaneous or induced); illustration of the main behavioral, cognitive, and motor assays applicable in laboratory animals for assessing the efficacy and potential toxicity of the drug under investigation; presentation of an example of preclinical drug design for the treatment of amyotrophic lateral sclerosis; brief outline of the steps required to move from preclinical studies to clinical application.

RECOMMENDED READING/BIBLIOGRAPHY

For both the Drug Design and Experimental Pharmacology modules, no official textbooks are available. The instructors will provide the slides and literature materials (in English).

TEACHERS AND EXAM BOARD

LESSONS

LESSONS START

The timetable for this course can be found at: EasyAcademy Portal, second semester.

Class schedule

DRUG DESIGN AND EXPERIMENTAL PHARMACOLOGY (INTEGRATED COURSE)

EXAMS

EXAM DESCRIPTION

The exam will consist of an oral test concerning some topics covered in classroom. The exam will be held at the same time as the other module. The grade will be the average of the grades obtained in the two modules.

ASSESSMENT METHODS

During the exam, students must demonstrate the knowledge acquired during the course, also by making connections with competencies gained in related disciplines. They will also be able to discuss the exam topics using appropriate scientific language.

FURTHER INFORMATION

Contact the teacher for further information not included in the teaching sheet.