MARIO VARASI
Education and PHD/Masters/Courses
1970-1976: Doctoral studies (laureato) in Medicinal Chemistry and Technology, University of
Rome, Italy [110/110 summa cum laude].
1977-1979: Post-doctoral research fellow, Institute of Organic Chemistry, Syntex ResearchPalo Alto, CA-USA
Titles (included other positions covered)
1979-1981 Organic Chemistry Lab. Head, R&D-Zambeletti SpA, Baranzate di Bollate,
Milano-Italy.
1981-1983 Organic Chemistry Lab. Head, Preclinical Research-Dow Lepetit, Via Durando, 38.
Milano, Italy.
1983-1994 CNS-Med. Chemistry Lab. Head, R&D Farmitalia Carlo Erba, Via Imbonati, 24.
Milano, Italy.
1994-1996 CNS-Med. Chemistry Department Head-Pharmacia & Upjohn, Viale Pasteur, 10.
Nerviano (MI), Italy
1997 Deputy Director of the Chemistry Department and acting Director of
Preclinical CNS Research, Pharmacia & Upjohn- Nerviano (MI), Italy.
1998-2005 Director of Chemistry Department, Discovery Research Oncology
Pharmacia and Pharmacia Italia S.p.A.-Pfizer Group, and Nerviano Medical
Sciences. Nerviano (MI), Italy.
2005- 2009 Director of Chemistry Department, Genextra S.p.A. Milano
(Italy)
Clinical Activities carried out at IEO
NA
Research Activities carried out at IEO
2009-present: Director of Drug Discovery Unit-Dept. of Experimental Oncology
(Epigenetics, Cancer Stem cell)
Passed Clinical and Research Activities
• Design and synthesis of novel antidepressant agents, anticonvulsants, 5-HT3 antagonists ,
antiexcitotoxin agents (EAA antagonists and kynurenine-3-hydroxylase inhibitors) and Abeta peptide aggregation inhibitors for Alzheimer.
• Project Leader for the following projects:
-5-HT3 antagonists (clinical candidate identified),
-antiexcitotoxin agents (NMDA antagonists and Kynurenine pathway interfering agents)
-anticonvulsants (clinical candidates identified).
-antiexcitotoxin agents.
Contribution to the discovery and identification of clinical candidates in the areas of epilepsy,
parkinson and neuropatic pain.
• Discovery and development of molecular targeted anticancer agents, development of
targeted libraries for the kinase platform.
Contribution to the discovery and identification of clinical candidates in the area of CDK2,
CDC7 and Aurora, and HDAC inhibitor and mitochondrial medicine.
• Experience of leading Department(s) of up to 120 scientists (Medicinal Chemistry, Analytical
Chemistry, Combinatorial Chemistry, Structural Chemistry, Molecular Modeling & Design
and Research Informatics-Biochemistry, Cell Biology and In vivo pharmacology).
• Focus on the optimisation of workflow and resource utilization, recruit and retain first class
scientists to secure optimal support of the drug discovery process.
• Author of ≈80 papers and holder of ≈80 patents.
Awards and other Recognitions
-Recipient of the Upjohn Award (2001).“Based upon demonstration of the Best-Managed
Behaviors and special accomplishments”
- Recipient of the “Medaglia G Giacomello” Soc. Chim. Italiana_Div. Di Chimica Farmaceutica
(2012) for his many and important contributions to the advancement of Medicinal Chemistry in
a long, distinguished and varied career as an industrial medicinal chemistry researcher.
Publications
1. Florian Thaler, Mario Varasi, Giacomo Carenzi, Andrea Colombo, Agnese Abate, Chiara
Bigogno, Roberto Boggio, Simone Carrara, Tiziana Cataudella, Roberto Dal Zuffo,
Veronica Reali, Stefania Vultaggio, Giulio Dondio, Stefania Gagliardi, Saverio Minucci,
Ciro Mercurio Spiro[chromane-2,4′-piperidine]-Based Histone Deacetylase
Inhibitors with Improved in vivo Activity ChemMedChem (2012), 7(4), 709-721.
2. Giuseppe La Regina, Ruoli Bai, Willeke Rensen, Antonio Coluccia, Francesco Piscitelli,
Valerio Gatti, Alessio Bolognesi, Antonio Lavecchia, Ilaria Granata, Amalia Porta, Bruno
Maresca, Alessandra Soriani, Maria Luisa Iannitto, Marisa Mariani, Angela Santoni,
Andrea Brancale, Cristiano Ferlini, Giulio Dondio, Mario Varasi, Ciro Mercurio, Ernest
Hamel, Patrizia Lavia, Ettore Novellino, and Romano Silvestri Design and Synthesis
of 2-Heterocyclyl-3-arylthio-1H-indoles as Potent Tubulin Polymerization and
Cell Growth Inhibitors with Improved Metabolic Stability Journal of Medicinal
Chemistry (2011), 54(24), 8394–8406.
3. Varasi, Mario; Thaler, Florian; Abate, Agnese; Bigogno, Chiara; Boggio, Roberto;
Carenzi, Giacomo; Cataudella, Tiziana; Dal Zuffo, Roberto; Fulco, Maria Carmela; Rozio,
Marco Giulio; Mai, Antonello; Dondio, Giulio; Minucci, Saverio; Mercurio, Ciro.
Discovery, Synthesis, and Pharmacological Evaluation of Spiropiperidine
Hydroxamic Acid Based Derivatives as Structurally Novel Histone Deacetylase
(HDAC) Inhibitors. Journal of Medicinal Chemistry (2011), 54(8), 3051-3064.
4. Barker, John J.; Barker, Oliver; Courtney, Stephen M.; Gardiner, Mihaly; Hesterkamp,
Thomas; Ichihara, Osamu; Mather, Owen; Montalbetti, Christian A. G. N.; Muller,
Annett; Varasi, Mario; Whittaker, Mark; Yarnold, Christopher J. Discovery of a novel
Hsp90 inhibitor by fragment linking. ChemMedChem (2010), 5(10), 1697-1700
5. Thaler, Florian; Colombo, Andrea; Mai, Antonello; Amici, Raffaella; Bigogno, Chiara;
Boggio, Roberto; Cappa, Anna; Carrara, Simone; Cataudella, Tiziana; Fusar, Fulvia;
Gianti, Eleonora; di Ventimiglia, Samuele Joppolo; Moroni, Maurizio; Munari, Davide;
Pain, Gilles; Regalia, Nickolas; Sartori, Luca; Vultaggio, Stefania; Dondio, Giulio;
Gagliardi, Stefania; Minucci, Saverio; Mercurio, Ciro; Varasi, Mario. Synthesis and
Biological Evaluation of N-Hydroxyphenylacrylamides and N-Hydroxypyridin-2ylacrylamides as Novel Histone Deacetylase Inhibitors. Journal of Medicinal
Chemistry (2010), 53(2), 822-839.
6. Barker, John J.; Barker, Oliver; Boggio, Roberto; Chauhan, Viddhata; Cheng, Robert K.
Y.; Corden, Vincent; Courtney, Stephen M.; Edwards, Neil; Falque, Virginie M.; Fusar,
Fulvia; Gardiner, Mihaly; Hamelin, Estelle M. N.; Hesterkamp, Thomas; Ichihara,
Osamu; Jones, Richard S.; Mather, Owen; Mercurio, Ciro; Minucci, Saverio; Montalbetti,
Christian A. G. N.; Muller, Annett; Patel, Deepti; Phillips, Banu G.; Varasi, Mario;
Whittaker, Mark; Winkler, Dirk; Yarnold, Christopher J. Fragment-based
Identification of Hsp90 Inhibitors. ChemMedChem (2009), 4(6), 963-966
7. Menichincheri, Maria; Bargiotti, Alberto; Berthelsen, Jens; Bertrand, Jay A.; Bossi,
Roberto; Ciavolella, Antonella; Cirla, Alessandra; Cristiani, Cinzia; Croci, Valter;
D'Alessio, Roberto; Fasolini, Marina; Fiorentini, Francesco; Forte, Barbara; Isacchi,
Antonella; Martina, Katia; Molinari, Antonio; Montagnoli, Alessia; Orsini, Paolo; Orzi,
Fabrizio; Pesenti, Enrico; Pezzetta, Daniele; Pillan, Antonio; Poggesi, Italo; Roletto,
Fulvia; Scolaro, Alessandra; Tato, Marco; Tibolla, Marcellino; Valsasina, Barbara;
Varasi, Mario; Volpi, Daniele; Santocanale, Corrado; Vanotti, Ermes. First Cdc7
Kinase Inhibitors: Pyrrolopyridinones as Potent and Orally Active Antitumor
Agents. 2. Lead Discovery. Journal of Medicinal Chemistry (2009), 52(2), 293307
8. Vanotti, Ermes; Amici, Raffaella; Bargiotti, Alberto; Berthelsen, Jens; Bosotti, Roberta;
Ciavolella, Antonella; Cirla, Alessandra; Cristiani, Cinzia; D'Alessio, Roberto; Forte,
Barbara; Isacchi, Antonella; Martina, Katia; Menichincheri, Maria; Molinari, Antonio;
Montagnoli, Alessia; Orsini, Paolo; Pillan, Antonio; Roletto, Fulvia; Scolaro, Alessandra;
Tibolla, Marcellino; Valsasina, Barbara; Varasi, Mario; Volpi, Daniele; Santocanale,
Corrado. Cdc7 Kinase Inhibitors: Pyrrolopyridinones as Potential Antitumor
Agents. 1. Synthesis and Structure-Activity Relationships. Journal of Medicinal
Chemistry (2008), 51(3), 487-501
9. Fancelli, Daniele; Moll, Juergen; Varasi, Mario; Bravo, Rodrigo; Artico, Roberta; Berta,
Daniela; Bindi, Simona; Cameron, Alexander; Candiani, Ilaria; Cappella, Paolo;
Carpinelli, Patrizia; Croci, Walter; Forte, Barbara; Giorgini, Maria Laura; Klapwijk, Jan;
Marsiglio, Aurelio; Pesenti, Enrico; Rocchetti, Maurizio; Roletto, Fulvia; Severino, Dino;
Soncini, Chiara; Storici, Paola; Tonani, Roberto; Zugnoni, Paola; Vianello, Paola.
1,4,5,6-Tetrahydropyrrolo[3,4-c]pyrazoles: Identification of a Potent Aurora
Kinase Inhibitor with a Favorable Antitumor Kinase Inhibition Profile. Journal
of Medicinal Chemistry (2006), 49(24), 7247-7251
10. Soncini, Chiara; Carpinelli, Patrizia; Gianellini, Laura; Fancelli, Daniele; Vianello, Paola;
Rusconi, Luisa; Storici, Paola; Zugnoni, Paola; Pesenti, Enrico; Croci, Valter; Ceruti,
Roberta; Giorgini, Maria Laura; Cappella, Paolo; Ballinari, Dario; Sola, Francesco;
Varasi, Mario; Bravo, Rodrigo; Moll, Juergen. PHA-680632, a Novel Aurora Kinase
Inhibitor with Potent Antitumoral Activity. Clinical Cancer Research (2006),
12(13), 4080-4089
11. Pevarello, Paolo; Brasca, Maria Gabriella; Orsini, Paolo; Traquandi, Gabriella; Longo,
Antonio; Nesi, Marcella; Orzi, Fabrizio; Piutti, Claudia; Sansonna, Pietro; Varasi, Mario;
Cameron, Alexander; Vulpetti, Anna; Roletto, Fulvia; Alzani, Rachele; Ciomei, Marina;
Albanese, Clara; Pastori, Wilma; Marsiglio, Aurelio; Pesenti, Enrico; Fiorentini,
Francesco; Bischoff, Jim R.; Mercurio, Ciro. 3-Aminopyrazole Inhibitors of
CDK2/Cyclin A as Antitumor Agents. 2. Lead Optimization. Journal of Medicinal
Chemistry (2005), 48(8), 2944-2956.
12. Fancelli, Daniele; Berta, Daniela; Bindi, Simona; Cameron, Alexander; Cappella, Paolo;
Carpinelli, Patrizia; Catana, Cornel; Forte, Barbara; Giordano, Patrizia; Giorgini, Maria
Laura; Mantegani, Sergio; Marsiglio, Aurelio; Meroni, Maurizio; Moll, Juergen; Pittala,
Valeria; Roletto, Fulvia; Severino, Dino; Soncini, Chiara; Storici, Paola; Tonani,
Roberto; Varasi, Mario; Vulpetti, Anna; Vianello, Paola. Potent and selective Aurora
inhibitors identified by the expansion of a Novel scaffold for protein kinase
inhibition. Journal of Medicinal Chemistry (2005), 48(8), 3080-3084.
13. Pevarello, Paolo; Bonsignori, Alberto; Dostert, Philippe; Heidempergher, Franco;
Pinciroli, Vittorio; Colombo, Maristella; McArthur, Robert A.; Salvati, Patricia; Post,
Claes; Fariello, Ruggero G.; Varasi, Mario. Synthesis and Anticonvulsant Activity
of a New Class of 2-[(Arylalkyl)amino]alkanamide Derivatives. Journal of
Medicinal Chemistry (1998), 41(4), 579-590.
14. Heidempergher, Franco; Pillan, Antonio; Pinciroli, Vittorio; Vaghi, Fabrizio; Arrigoni,
Claudio; Bolis, Giorgio; Caccia, Carla; Dho, Luciano; McArthur, Robert; Varasi, Mario.
Phenylimidazolidin-2-one Derivatives as Selective 5-HT3 Receptor Antagonists
and Refinement of the Pharmacophore Model for 5-HT3 Receptor Binding.
Journal of Medicinal Chemistry (1997), 40(21), 3369-3380.
15. Tagliavini, F.; McArthur, R. A.; Canciani, B.; Giaccone, G.; Porro, M.; Bugiani, M.;
Lievens, P. M.-J.; Bugiani, O.; Peri, E.; Dall'Ara, P.; Rocchi, M.; Poli, G.; Forloni, G.;
Bandiera, T.; Varasi, M.; Suarato, A.; Cassutti, P.; Cervini, M. A.; Lansen, J.; Salmona,
M.; Post, C. Effectiveness of anthracycline against experimental prion disease
in Syrian hamsters. Science (Washington, D. C.) (1997), 276(5315), 1119-1122.
Congresses
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Member of the Organizing Committee of the European Advanced School of Medicinal
Chemistry in Urbino (1995-2011)
Elected Member of the Board of the “Divisione di Chimica Farmaceutica-Società Chimica
italiana” [2007-2009 and 2010-2012]
Member of the Scientific Committee of the National Congress of Medicinal Chemistry (20072013)
Member of the International Scientific Committee of XXIIIrd International Symposium on
Medicinal Chemistry (EFMC-ISMC 2014),