DC 14: Lucilla Paretti
Lucilla Paretti (Italy) studied Pharmaceutical Chemistry and Technology at the University of Siena (Italy). Her thesis work focused on the design and synthesis of nitrogen heterocyclic compounds as novel modulators of the Pseudomonas aeruginosa Quorum Sensing system, targeting the transcriptional regulator PqsR.
As part of the Erasmus+ Program, she joined the University of Eastern Finland, where she contributed to a research project entitled “Design and Synthesis of Chemical Tools to Explore the Kinome and Interrogate the Biology of Understudied Kinase Targets” synthetizing kinase inhibitors and participating in the chemical exploration of the kinome. She continued her work at the same institution as a Project Researcher.
Her academic journey has been complemented by practical experiences in pharmacy operations and international exposure through a cultural and linguistic immersion in Switzerland.
Planned secondments: 1 month at the University of Basel to learn complementary covalent targeting approaches; 1 month at PD-value for modelling of PK/PD properties; 3 months at BiosolveIT for structure-based drug design
University of Basel
1 monthBasel, Switzerland
PD-Value
1 month Utrecht, Netherlands
BioSolveIT
3 monthsSankt Augustin, Germany
My research project
The p70 ribosomal protein S6 kinases S6K1 (RPS6KB1) and S6K2 (RPS6KB2) are major downstream effectors of the mTOR complex 1 (mTORC1). While the role of S6K1 is well studied, at least in cancer, knowledge on S6K2 function remains severely limited, especially in the context of mTORopathies. Investigation of S6K2 as a potential drug target is hampered by a lack of isoform-selective S6K2 inhibitors to dissect S6K1 and S6K2 functions. We recently reported the first selective S6K2 inhibitor which relies on a S6K2-specific covalent binding mechanism. DC14 aims at optimizing our S6K2 inhibitors for application in vivo, with a special emphasis in brain penetration. DC14 will improve the solubility and identify/mitigate metabolic hotspots, while maintaining potency and selectivity. In conjunction with molecular modelling, optimization will be guided by enzyme and reactivity assays, physicochemical property profiling and testing of in vitro absorption, distribution, metabolism, and excretion (ADME) properties (e.g. microsomal stability, permeability and efflux). In vivo PK/PD profiling of key compounds will be performed with collaborators from this consortium and the optimized inhibitors will be provided to partners for functional in vivo studies.
PhD enrolment : 
DC 13: Christina Maria Kazakou