72964 - Research and Development of Drugs and Small Molecules

Learning outcomes

At the end of the course the student acquires the basic chemical-pharmaceutical knowledge on the approaches and methodologies currently used in the pharmaceutical industry in the discovery and development of new drugs, as well as innovative approaches for drugs under investigation. In particular, the student is able to know the peculiar aspects concerning the design and the mechanism of action at the molecular level of drugs having the structure of "small molecules".

Course contents

The Drug discovery process in the post-genomic era.

Biological macromolecules as drug targets: proteins, (enzymes, structural and carrier proteins, ion pumps, ion channels, membrane and intracellular receptors), nucleic acids, lipids, carbohydrates.

Ion channel receptor superfamily: classification and models. The nicotinic receptor (LGIC): channel structural and functional organization; development of competitive and non-competitive agonists for the treatment of neurological disorders. Philanthotoxins and the concept of chemical probe. Vanilloid receptors: channel structural and functional organization; development of agonist and antagonists for the treatment of pain.

GPCR superfamily: classification and models. The muscarinic receptor: structural organization and functional domains; development of allosteric/bitopic modulators for the treatment of Alzheimer's disease.

Intracellular receptor superfamily: classification and models. The estrogen receptor: structural organization of the ligand binding pocket (LBP) and receptor conformational states; development of agonists, antagonists and SERMs.

Tyrosine kinase receptor superfamily : classification and models. The epidermal growth factor receptor: ATP binding site topology. Development of catalytic site inhibitors: from competitive to covalent inhibitors. Paradigm shift from selective to multi-target ligands. Smart chemotherapy: small molecules vs antibodies.

Readings/Bibliography

Slides and lecture notes, selected references will be provided during the class

Teaching methods

Lectures in class (Tutor Presentation and Tutor-Guided Group Discussion)

Assessment methods

A comprehensive final viva voce examination, meant to assess the skills acquired during the course, is given. The exam is organized in 2 parts. In the first part the student exposes a topic of his choice (the aim is to verify the exposition/technical vocabulary/reasoning skills on a well-studied topic). In the second part a question on any topic of the program is made (to verify the overall preparation of the student).

Teaching tools

The teaching material (slides) presented during classes is available on the Virtuale platform.

Office hours

See the website of Maria Laura Bolognesi