IFOM Experimental Therapeutics Program

Experimental Therapeutics Program

Mario Varasi

Mario Varasi

Mario Varasi obtained the degree in CTF in Rome in 1976, followed by two years postdoctoral fellowship in the Institute of Organic Chemistry at Syntex Research in Palo Alto, California.
Mario Varasi has more than 35 years of drug discovery research experience with Zambeletti, Dow-Lepetit, Farmitalia (then Pharmacia, Pharmacia&Upjohn, Pfizer, NMS) and Genextra.
In 2009 he joined the European Institute of Oncology as co-founder and Director of the Drug Discovery Program. Since April 1st, 2016 he is Director of the Experimental Therapeutics Program at IFOM (the FIRC Institute of Molecular Biology) in Milan.
His main area of research were in the CNS area (antidepressants agents, anticonvulsants, 5-HT3 antagonists, antiexcitotoxin agents and A-beta peptide aggregation inhibitors for Alzheimer) and then in the Oncology field (kinase and Hsp90, cancer metabolism, cancer stem cell and epigenetics).
Co-Inventor and Discovery Co-Project Leader for Safinamide (now on the market as Xadago, for the treatment of idiopathic Parkinson’s disease), he contributed to the discovery of several development candidates including multiple Phase I and II assets for CNS and Oncology. He is author of 96 papers and holder of 85 patents.

Over the past years, there have been major advances in many of the scientific and technological inputs into drug research and development (R&D). These dramatic improvements should have tended to increase the efficiency of the R&D process. Instead the number of new drugs introduced per year has been broadly flat over the period since the 1950s, while R&D investments have grown fairly steadily. The success rate of R&D projects is very low. Only about 1.8 % of projects succeed from target discovery all the way to product launch. The bottleneck in R&D are the complexity of disease biology, lack of accurate and efficient methods for target identification/validation, lack of "continuous validation process" of the targets and lack of accurate and efficient methods for patient stratification. To focus on these issues and to combine excellence in basic science in the strongly knowledge-based environment of academic research with industrial drug discovery experience represents the IFOM strategies toward improving successes and innovations in drug research.

The primary objective of the Experimental Therapeutic Program (ETP) is to translate the basic research developed in IFOM into drug discovery projects. The ETP scientists work in close collaboration with IFOM Principal Investigators in state-of-the-art laboratories to identify and develop new therapeutics for unmet medical need. The ETP is the team devoted to the design, synthesis and biological evaluation of small molecules having the desired activity/specificity against the targets of interest. The development of these small molecules is an iterative process generated by innovative biochemical, cellular and in vivo assays to understand their functional roles , and to rank and select them up to the identification of a preclinical candidate.

To reach its goals the ETP has access to different state-of-the-art technologies including traditional and parallel medicinal chemistry, automated purification system of compounds, automated work station for biochemistry and cellular assays, array scan high content systems, liquid handler for compound plate preparation, integrated chemoinformatic system to handle chemical, analytical and biological data, tools for modeling, structure-based drug design and docking and scoring, and access to a chemical collection comprising commercially available compounds, focused chemical libraries, fragments and proprietary molecules. Current area of interest includes projects targeting DNA repair and in DNA damage response, cellular motility, ubiquitin pathway, drug repositioning and development of innovative technologies.

Laboratory location: Milan, Italy

Recent patents

  • Pasqualato, Sebastiano; Pasi, Maurizio; Amici, Raffaella; Varasi, Mario; Mercurio, Ciro; Sartori, Luca; Polo, Simona; Maspero, Elena; Faga, Giovanni
    Hect e3 ligase inhibitors and uses thereof
    PCT Int. Appl. (2020), WO 2020245213 A1 20201210
  • Varasi, Mario; Cappa, Anna; Vianello, Paola; Moretti, Loris; Sartori, Luca; Mercurio, Ciro
    Thieno[2,​3-​b]​pyrrole and thieno[3,​2-​b]​pyrrole derivatives as histone demethylase inhibitors and their preparation
    PCT Int. Appl. (2019), WO 2019034774 A1 20190221
  • Varasi, Mario; Villa, Manuela; Trifiró, Paolo; Fancelli, Daniele; Mercurio, Ciro; Vianello, Paola; Sartori, Luca
    Oxime derivatives useful as inhibitors of histone demethylase KDM4C and their preparation
    PCT Int. Appl. (2017), WO 2017198785 A1 20171123.
  • Vianello, Paola; Romussi, Alessia; Cappa, Anna; Trifiró, Paolo; Varasi, Mario; Sartori, Luca; Mercurio, Ciro
    Preparation of imidazol-2-ylthienopyrrole compounds as histone demethylase inhibitors
    PCT Int. Appl. (2017), WO 2017198780 A1 20171123.

Program members

Head of Chemistry
VARASI Mario (a.i.)
Analytical Chemistry
FATTORI Raimondo
Computational Sciences
Medicinal Chemistry
AMICI Raffaella
MERONI Giuseppe
PASI Maurizio
VILLA Manuela
Head of Biology
Biochem./Molec. Biol./In vivo Pharmac.
CERA M. Rosaria
CIRÒ Marco

Recent publications

  • Zwergel, Clemens; Di Bello, Elisabetta; Fioravanti, Rossella; Conte, Mariarosaria; Nebbioso, Angela; Mazzone, Roberta; Brosch, Gerald; Mercurio, Ciro; Varasi, Mario; Altucci, Lucia; Valente, Sergio; Mai, Antonello
    Novel Pyridine-Based Hydroxamates and 2'-Aminoanilides as Histone Deacetylase Inhibitors: Biochemical Profile and Anticancer Activity
    ChemMedChem (2021), 16(6), 989-999.
  • Roberto Ravasio, Elena Ceccacci, Luciano Nicosia, Amir Hosseini, Pier Luigi Rossi, Iros Barozzi, Lorenzo Fornasari, Roberto Dal Zuffo, Sergio Valente, Rossella Fioravanti, Ciro Mercurio, Mario Varasi, Andrea Mattevi, Antonello Mai, Giulio Pavesi,Tiziana Bonaldi, Saverio Minucci
    Targeting the scaffolding role of LSD1 (KDM1A) poises acute myeloid leukemia cells for retinoic acid–induced differentiation
    Science advances (2020), 6(15), eaax2746
  • Romussi, Alessia; Cappa, Anna; Vianello, Paola; Brambillasca, Silvia; Cera, Maria Rosaria; Dal Zuffo, Roberto; Faga, Giovanni; Fattori, Raimondo; Moretti, Loris; Trifiro, Paolo; et al
    Discovery of Reversible Inhibitors of KDM1A Efficacious in Acute Myeloid Leukemia Models
    ACS Medicinal Chemistry Letters (2020), 11(5), 754-759.
  • Ravasio, Roberto; Ceccacci, Elena; Nicosia, Luciano; Hosseini, Amir; Rossi, Pier Luigi; Barozzi, Iros; Fornasari, Lorenzo; Zuffo, Roberto Dal; Valente, Sergio; Fioravanti, Rossella; Mercurio, Ciro; Varasi, Mario; Mattevi, Andrea; Mai, Antonello; Pavesi, Giulio; Bonaldi, Tiziana; Minucci, Saverio
    Targeting the scaffolding role of LSD1 (KDM1A) poises acute myeloid leukemia cells for retinoic acid-​induced differentiation
    Science Advances (2020), 6(15), eaax2746.