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Simona Collina completed graduation cum laude in Medicinal Chemistry and Pharmaceutical Technology in 1989, from University of Pavia, Italy. In December 1989 - January 1992, was researcher at the laboratory “Analytical researches” of SPA (Società Prodotti Antibiotici) Milan. From 1992-2001, was assistant professor (SSD CHIM/08), Faculty of Pharmacy, University of Pavia 2001-ongoing, Associate Professor SSD CHIM/08 Department of drug Sciences, University of Pavia 2017 National Habilitation for Full Professor of Medicinal Chemistry (CHIM/08) – Italian Ministry of Research and University.
Sigma Receptors (SRs) represent an interesting orphan class of molecular targets to hit for counteracting neurodegenerative diseases and cancer. They can be divided into two receptor subtypes (S1R and S2R, respectively), endowed with different physio-pathological and structural properties. From a therapeutic standpoint, the pharmacological activity of S1Rs is strictly related to the modulators that they interact with. In detail, S1R agonists promote neuroprotection and neuroplasticity, whereas antagonists can be beneficial in thwarting neuropathic pain and tumorous manifestations. Conversely, S2R modulators may have a pivotal role as anticancer agents. So far, four compounds reached the Clinical Stage of the Drug Discovery Process, as drug candidate in therapy and diagnosis for Alzheimer’s disease (ANAVEX 2-73, AVP-923), for neuropathic pain (MR309) and cancer ([18F]-ISO-1). The Medicinal Chemistry Laboratory (MedChemLab) is part of this scenario and has a long lasting experience in this field. Indeed, the group spent its efforts in designing and synthetizing molecules with affinity and selectivity towards SRs and discoved (R)-RC-33 and RC-106 as promising compounds. (R)-RC-33 is a S1R agonist compound, characterized by good S1R affinity, good in vivo pharmacokinetic profile and endowed with neuroprotective properties. RC-106 is a pan-SR ligand (S1R antagonist and S2R agonist) showing anticancer activity towards a panel of cancer cell lines. These encouraging results lead members of the MedChemLab group to keep believing that SR modulators could become a relevant opportunity in the pharmaceutical field. Accordingly, throughout this speech the state-of-art and new insights of SRs, as well as the MedChemLab projects will be depicted.