- Curriculum Vitae
Education, position and didactics
Laurea (M.S.) in Pharmaceutical Chemistry and Technology (Chimica e Tecnologia Farmaceutiche, C.T.F.) cum laude at the Faculty of Pharmacy of the University of Parma (Italy) in 1990. Lecturer at the Faculty of Pharmacy of the same University in 1993. Associate Professor of Medicinal Chemistry in 2000. Full Professor of Medicinal Chemistry at the Faculty of Pharmacy since 2001.
Teaching activity includes the courses of "Chimica Farmaceutica I" (Medicinal Chemistry, 1st course) and "Laboratorio di progettazione e sintesi dei farmaci" (Laboratory of drug design and Synthesis), held for the degree in C.T.F. at the 3rd and 4th year, respectively. He had been President of the teacher board of the "Corso di Laurea Specialistica in C.T.F." at the University of Parma from 2005 to 2008.
Commitments, and honors
Coordinator of the PhD course (Dottorato) of "Scienze del farmaco, delle biomolecole e dei prodotti per la salute" at the Dipartimento di Scienze degli Alimenti e del Farmaco in Parma (2013-present).
Director of the PhD School (Scuola dottorale) of "Scienze biologiche, farmaceutiche ed alimentari" at University of Parma (2017-present).
Member of the Scientific Committee of the European School of Medicinal Chemistry (2011-2017).
Member of the Executive Committee of the ULLA Consortium od European Schools of Pharmacy.
Member of the Editorial Board of the scientific journals ChemMedChem and Cannabis and Cannabinoid Research.
Invited speaker at Summer School in Biotechnology (Gdansk, 2014); XXV Congresso Nazionale della Società Chimica Italiana (Rende 2014), New Perspective in Medicinal Chemistry (NPCF 8, Parma 2014); Centre Europeen de Calcul Atomique et Moleculaire (CECAM) workshops (Lausanne, 2013 and 2011); XXIV Congresso Nazionale della Società Chimica Italiana (Lecce 2011); Italian-Spanish-Portuguese Joint Meeting in Medicinal Chemistry (Palermo 2018).
Coordinator of the local unit at University of Parma of the project: "ONCOPENTA: Oncologia di Precisione e Nuove Terapie Antitumorali", financed by the Region Emilia-Romagna in 2016. Coordinator of the medicinal chemistry unit in the project "Beyond third-generation TKI in EGFR mutated NSCLC: resistance mechanisms, novel combinations and synthesis of new agents", financed by AIRC in 2017.
Principal Investigator and National coordinator of the National Research project (Prin) "Exploiting the EndoCannabinoid System to control inflammation and promote neuroprotection and myelin repair (ExECS)" 2019
Author of more than 200 articles on international scientific journals, which received more than 9000 citations (H-index 48).
He is inventor in more than 15 international patent applications, with 3 Patents issued in the USA (No. 8,003,693, 2011; 8,791,163, 2014; 9,187,413, 2015).
After three years (1990-1993) spent in the Glaxo (then GSK) Drug Design Center (Verona, Italy) I setup a research group of computational medicinal chemistry at the University of Parma.
At present, my research group at Dipartimento di Farmacia in Parma includes a molecular modelling and drug-design section, a laboratory of synthetic chemistry and a section of analytical chemistry. Combining these competences, and collaborating with external groups, we performed the design, synthesis and characterization of new compounds with different biological activities, spanning from histaminergic and melatoninergic actions to antiproliferative or endocannabinoid-modulating activity. Within a long collaboration with the group of Daniele Piomelli at UCI, and of Giorgio Tarzia at the University of Urbino, we participated to the discovery and development of novel and often remarkable inhibitors of different enzymes involved in endocannabinoid inactivation, MGL, FAAH and NAAA. Remarkable results have been achieved by the group also in the field of melatoninergic agents. Attention is dedicated to the study of physicochemical and pharmacokinetic (ADME) properties of drug candidates, and their influence on access to the CNS and metabolic stability.
Contribution to science
Within a collaboration with the groups of Daniele Piomelli at UCI and Giorgio Tarzia in Urbino, modelling studies on the reaction mechanism of carbamate-based inhibitors of FAAH, the enzyme mainly responsible of inactivation of the endocannabinoid anandamide, helped the rational design of new compounds and led to the discovery of the reference inhibitor URB597 and to the development of less reactive derivatives, including URB694 and URB937. These compounds became milestones in the study of pharmacological effects of FAAH inhibition.
1. Kathuria S., Gaetani S., Fegley D., Valino F., Duranti A., Tontini A., Mor M., Tarzia G., La Rana G., Calignano A., Giustino A., Tattoli M., Palmery M., Cuomo V., Piomelli D. 2003. Modulation of anxiety through blockade of anandamide hydrolysis. Nature Medicine 9. 76. (Cited 1052 times)
2. Mor M, Rivara S, Lodola A, Plazzi PV, Tarzia G, Duranti A, Tontini A, Piersanti G, Kathuria S, Piomelli D, 2004. Cyclohexylcarbamic acid 3 '- or 4 '-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: Synthesis, quantitative structure-activity relationships, and molecular modeling studies. Journal Of Medicinal Chemistry 47. 4998-5008. (Cited 209 times).
3. Clapper J. R., Moreno-Sanz G., Russo R., Guijarro A., Vacondio F., Duranti A., Tontini A., Sanchini S., Sciolino N. R., Spradley J. M., Hohmann A. G., Calignano A., Mor M., Tarzia G., Piomelli D., 2010. Anandamide suppresses pain initiation through a peripheral endocannabinoid mechanism. Nature Neuroscience 13. 1265-1270. (Cited 172 times).
In collaboration with Daniele Piomelli, we discovered pharmacological agents that target 2-AG deactivation. Our experience and competence in the design of cysteine-addressing agents could be proficuous for the development and optimization of new compounds that modulate MGL activity with an allosteric mechanism, interacting with the regulatory cysteines expressed on its surface.
1. A.G. Hohmann, R.L. Suplita II, N.M. Bolton, M.H. Neely, D. Fegley, R. Mangieri, J.F. Krey, J.M. Walker, P.V. Holmes, J.D. Crystal, A. Duranti, A. Tontini, M. Mor, G. Tarzia and D. Piomelli, 2005. An endocannabinoid mechanism for stress-induced analgesia. Nature 435, 1108-1112. PMID: 15973410 (cited 506 times)
2. King A.R., Lodola A., Carmi C., Fu J., Mor M., Piomelli D., 2009. A critical cysteine residue in monoacylglycerol lipase is targeted by a new class of isothiazolinone-based enzyme inhibitors. British Journal of Pharmacology 157. 974-983. (Cited 63 times).
3. Scalvini L, Vacondio F, Bassi M, Pala D, Lodola A, Rivara S, Jung KM, Piomelli D, Mor M. 2016 Free-energy studies reveal a possible mechanism for oxidation-dependent inhibition of MGL. Scientific reports 6 31046.
The enzyme NAAA was recently discovered as responsible for the inactivation of bioactive fatty acid amides, including the anti-inflammatory palmitoylethanolamide (PEA). NAAA has an uncommon catalytic mechanism, with an N-terminal cysteine as the nuceophile, and its 3D structure is still not available. In spite of the potential of NAAA inhibitition in antiinflammatory therapy, till 2009 no significantly potent inhibitor was known. Within a collaboration with the groups of Daniele Piomelli at UCI and Giorgio Tarzia in Urbino, starting from a small library of compounds able to function as cysteine traps, and from molecular models and scientific speculation, we identified a class of beta-lactones that represented the first chemotype of potent NAAA inhibitors, and were further developed to similar classes of more druggable compounds.
1. Solorzano C., Zhu C., Battista N., Astarita G., Lodola A., Rivara S., Mor M., Russo R., Maccarrone M., Antonietti F., Duranti A., Tontini A., Cuzzocrea S., Tarzia G., Piomelli D., 2009. Selective N-acylethanolamine-hydrolyzing acid amidase inhibition reveals a key role for endogenous palmitoylethanolamide in inflammation. PNAS 106. 20966-20971. (Cited 136 times).
2. Solorzano C., Antonietti F., Duranti A., Tontini A., Rivara S., Lodola A., Vacondio F., Tarzia G., Piomelli D., Mor M., 2010. Synthesis and Structure-Activity Relationships of N-(2-Oxo-3-oxetanyl)amides as N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors. Journal Of Medicinal Chemistry 53. 5770-5781. (Cited 41 times).
Synthetic ligands at melatonin receptors have been regarded for many years as potential new drugs for the treatment of phase-shift disorders and depression. While compounds that have been finally introduced in the market are full agonist at both melatonin receptors, MT2-selective partial agonists have recently shown to improve sleep quality. Starting from a rational approach, we designed several classes of MTR ligands with high affinity and selectivity, and different levels of intrinsic activity. Some of these compounds are now among the best pharmacological agents available in the field for preclinical studies.
1. Rivara S., Lodola A., Mor M., Bedini A., Spadoni G., Lucini V., Pannacci M., Fraschini F., Scaglione F., Sanchez R.O., Gobbi G., Tarzia G. 2007. N-(substituted-anilinoethyl)amides: Design, synthesis, and pharmacological characterization of a new class of melatonin receptor ligands. Journal Of Medicinal Chemistry 50. 6618-6626. (Cited 58 times).
2. Ochoa-Sanchez R., Comai S., Lacoste B., Bambico F.R., Dominguez-Lopez S., Spadoni G., Rivara S., Bedini A., Angeloni D., Fraschini F., Mor M., Tarzia G., Descarries L., Gobbi G. 2011. Promotion of non-rapid eye movement sleep and activation of reticular thalamic neurons by a novel MT 2 melatonin receptor ligand. J. Neurosci. 31, 18439-18452. (Cited 48 times).
Irreversible inhibitors of tyrosin-kinases represent a common strategy to overcome resistance in antitumor therapy. At the same time, the acrylamide group, genrally present in such compounds, is remarkably reactive, with consistent risk of unwanted effects. Exploring the chemical space of warheads, we developed EGFR inhibitors that, while having a much less reactive functionality, irreversibly inhibit EGFR. In a xerograft model of gefitinib-resistant tumor, a 3-aminopropenamide derivative showed antiproliferative activity similar to that of an acrylamide-containing control drug, but with significanly lower toxicity. Recent investigations revealed the molecular mechanism of covalent inhibitors and of tumore resistance. Recently, new small molecules or peptides which show antiproliferative activity sequestering growth factors have been discovered.
1. Callegari D, Ranaghan KE, Woods CJ, Minari R, Tiseo M, Mor M, Mulholland AJ, Lodola A. L718Q mutant EGFR escapes covalent inhibition by stabilizing a non-reactive conformation of the lung cancer drug osimertinib. Chemical Science publised online, 2018
2. Ronca R, Giacomini A, Di Salle E, Coltrini D, Pagano K, Ragona L, Matarazzo S, Rezzola S, Maiolo D, Torrella R, Moroni E, Mazzieri R, Escobar G, Mor M, Colombo G, Presta M. Long-Pentraxin 3 Derivative as a Small-Molecule FGF Trap for Cancer Therapy. Cancer Cell 28 225-239; 2015. (Cited 24 times)
3. Carmi C., Galvani E., Vacondio F., Rivara S., Lodola A., Russo S., Aiello S., Bordi F., Costantino G., Cavazzoni A., Alfieri R. R., Ardizzoni A., Petronini P.G., Mor M., 2012. Irreversible Inhibition of Epidermal Growth Factor Receptor Activity by 3-Aminopropanamides. Journal Of Medicinal Chemistry 55. 2251-2264. (Cited 33 times).
Anno accademico di erogazione: 2021/2022
Anno accademico di erogazione: 2020/2021
Anno accademico di erogazione: 2019/2020
Anno accademico di erogazione: 2018/2019
Anno accademico di erogazione: 2017/2018
Anno accademico di erogazione: 2016/2017
- Course year: 3 - Full cicle (5 years) - Pharmaceutical chemistry and technology - A.Y.: 2014/2015
- Second cycle degree GENOMIC, MOLECULAR AND INDUSTRIAL BIOTECHNOLOGIES A.Y. 2021/2022
- DRUG SCIENCES A.Y. 2020/2021
- Second cycle degree GENOMIC, MOLECULAR AND INDUSTRIAL BIOTECHNOLOGIES A.Y. 2020/2021
- DRUG SCIENCES A.Y. 2019/2020
- Second cycle degree GENOMIC, MOLECULAR AND INDUSTRIAL BIOTECHNOLOGIES A.Y. 2019/2020
- Second cycle degree GENOMIC, MOLECULAR AND INDUSTRIAL BIOTECHNOLOGIES A.Y. 2018/2019
- Full cicle (5 years) Pharmaceutical chemistry and technology A.Y. 2017/2018
- Full cicle (5 years) Pharmaceutical chemistry and technology A.Y. 2016/2017
- Full cicle (5 years) Pharmaceutical chemistry and technology A.Y. 2015/2016
- Full cicle (5 years) Pharmaceutical chemistry and technology A.Y. 2014/2015
Chapter 9: Natural and Synthetic Agents That Target Intracellular Monoacylglycerol Lipase (MGL) ActivityYear: 2021Author/s: SCALVINI, Laura, RIVARA, Silvia, MOR, Marco, PIOMELLI, DANIELE
Benzisothiazolinone Derivatives as Potent Allosteric Monoacylglycerol Lipase Inhibitors That Functionally Mimic Sulfenylation of Regulatory CysteinesYear: 2020Author/s: CASTELLI, Riccardo, SCALVINI, Laura, VACONDIO, Federica, LODOLA, Alessio, ANSELMI, Mattia, CARMI, Caterina, BASSI, Michele, FERLENGHI, FRANCESCA, RIVARA, Silvia, MOR, Marco, PIOMELLI, DANIELE
Antidepressant-like effects of pharmacological inhibition of FAAH activity in socially isolated female ratsYear: 2020Author/s: CARNEVALI, Luca, STATELLO, ROSARIO IGNAZIO, VACONDIO, Federica, FERLENGHI, FRANCESCA, RIVARA, Silvia, MOR, Marco, SGOIFO, Andrea
Year: 2020Author/s: ELISI, GIAN MARCO, SCALVINI, Laura, CARMI, Caterina, BARTOLUCCI, Silvia, MOR, Marco, RIVARA, Silvia
FGF Trapping Inhibits Multiple Myeloma Growth through c-Myc Degradation-Induced Mitochondrial Oxidative StressYear: 2020Author/s: CASTELLI, Riccardo, MOR, Marco