B4084 - NEW CHEMICAL MODALITIES IN DRUG DISCOVERY

Conoscenze e abilità da conseguire

The course offers the opportunity to develop specific knowledge on the initial stages of the research and development of new drugs, including innovative ones. It aims to provide critical comprehension of the approaches underlying the rational design of new drugs and emerging modalities, even beyond traditional small molecules. At the end of the course the student will be able to evaluate the opportunities offered by the different therapeutic modalities to modulate certain drug targets and provide the most effective treatment for a given disease.

Basic knowledge of organic chemistry, molecular/cellular biology and/or pharmaceutical sciences is required.

Programma/Contenuti

1. Introduction to the drug discovery process. Target identification and validation. Hit identification. Hit-to-lead. Lead optimization.

2. Undruggable targets and new chemical modalities.

3. Network- and Poly-pharmacology.

4. Fragment-based drug discovery. The discovery of Balversa®.

5. RNA/oligonucleotide-based drugs: antisense oligonucleotides (ASOs – e.g., Spinraza®), aptamers (e.g., Macugen), RNA-based drugs (mRNA, e.g., Comirnaty®, RNAi – e.g., Oxlumo®).

6. Macrocycle/cyclopeptide-based drugs. Discovery of macrocycles/cyclopeptides-based drugs (e.g., Vonjo®, Olysio®).

7. Drug conjugates. Discovery of antibody-drug conjugates (e.g., Elahere™), small molecule drug conjugates (e.g., Lutathera®), fluorescent drug conjugates (e.g., Cytalux®).

8. Photoactivatable drugs. Introduction to photoactivable drugs: photosensitizers for photodynamic therapy (e.g., Photofrin®, 5ALA), "photoswitchable" drugs (e.g., KIO-301).

9. Degraders in the clinic and in clinical trials. Introduction to degraders: molecular glues (e.g., Thalomid®, Revlimid®), PROTACs (e.g., ARV-110, ARV-471), and other degraders (e.g., RIBOTACs).

Testi/Bibliografia

Bibliography relevant to the topics covered in the course:

Angew. Chem. Int. Ed. 2017, 56, 10294.

ACS Med. Chem. Lett. 2020, 11, 3, 228–231

Metodi didattici

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

Modalità di verifica dell'apprendimento

The “prova di idoneità” consists of a meeting following the end of the seminar in which each student will critical discuss one of the course topic in form of an essay or a power point presentation (about 1000 words or 4 slides). This can be individual or in team as long as the individual's contribution is clear and should to be agreed with the teacher in advance.

Strumenti a supporto della didattica

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

Orario di ricevimento

Consulta il sito web di Maria Laura Bolognesi