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Pharmacological modulation of innate immunity by small molecules: preclinical development of TLR4 agonists and antagonists

  • Dates: 6 December 2023, 15:00 - 16:00
  • Cost: Free
  • Venue: Online
Join us on Teams on 6 December at 3pm
A hand reaching for medical icons on a screen

Join ARU's Medical Technology Research Centre (MTRC) online for a seminar from Prof Francesco Peri (University of Milano-Bicocca) on innovative strategies to target inflammatory diseases and activate innate immunity.

While “biological” drug based on antibodies and nucleic acids allow unprecedented efficacy and selectivity in targeting tumours and inflammatory diseases, small molecules (“chemical” drugs) targeting innate immunity and inflammation circuits are still valuable tools for developing innovative anti-inflammatory agents, vaccine adjuvants and tumour immunotherapeutics.

Through about 20 years of multidisciplinary research in the field of Toll-Like Receptors (TLRs) modulation by synthetic and natural molecules, our group developed several innovative strategies to target inflammatory diseases and to activate innate immunity.

Several generation of glycolipids active as TLR4 antagonists and agonists allowed an extended analysis of cellular pathways selectively activated and deactivated with important pharmacological effects.

In this seminar the structure-activity relationship of TLR4 modulators will be presented and discussed in relation to activation/deactivation of the two major pathways related to TLRs action: the MyD88 pathway leading to inflammatory cytokines production and the TRAM/TRIF/IRF3 pathway inducing IFN-β synthesis. The action of synthetic compounds on NLRP3 inflammasome will be discussed as well.

The mechanism of action of TLR4 modulators and their preclinical development as vaccine adjuvants (Figure 1, below) and anti-inflammatory drugs will be presented.

Diagram showing the development of TLR4 agonists as vaccine adjuvants

Figure 1: Development of TLR4 agonists as vaccine adjuvants

Prof Francesco Peri is full Professor of Organic and Medicinal Chemistry at the University of Milano-Bicocca and at the Humanitas University (Milano). He also holds a permanent professorship at the Ecole Nationale Superieure (ENS) of Lyon (France).

Francesco is President of the MicrobiotaMi association, and Delegate of the Rector for the University of Innovation Foundation, an organisation devoted to the valorisation of innovation and to decisional support to university start-ups.

He is also Founder and Head of Scientific Board of the academic spin-off CP2 Biotech (March 2020), whose focus is the valorisation of new drug hits and the development of innovative therapeutic approaches to vaccine adjuvants and inflammatory diseases.

Francesco's research interests are drug discovery and development, and chemical biology, in particular the use of small organic molecules to interrogate biological systems.

His group developed and patented innovative modulators of the innate immunity receptor TLR4. Some of these compounds are in the preclinical phase of development as vaccine adjuvants, and a collaboration is ongoing with Croda/Avanti Lipids to enter the veterinary market.

Other first-in-class drug leads against heart failure Francesco and colleagues have discovered, in collaboration with the company Windtree (USA), are now in the clinical phase of development.

Francesco's group has published more than 120 papers and he is named as an inventor in more than 10 patents. He has delivered more than 50 invited lectures to international congresses, his H index is 37 (Scopus) / 42 (Google Scholar).

  • Dates: 6 December 2023, 15:00 - 16:00
  • Cost: Free
  • Venue: Online
Join us on Teams on 6 December at 3pm