HIT SELECTION STRATEGIES FOR IDENTIFICATION OF KINASE INHIBITORS MODULATING CIRCADIAN RHYTHM IN AD
Home institution: Hradec Kralove University - Czech Republic (24 months)
Host institution: Alma Mater Studiorum University of Bologna - Italy (10 months)
PhD Enrolment #1: Hradec Kralove University - Czech Republic
PhD Enrolment #2: Alma Mater Studiorum University of Bologna - Italy
Supervisor #1: Kamil Musilek
Supervisor #2: Manuela Bartolini
Intersectoral Secondment: Ankar Pharma – Spain
Objectives: University of Hradec Kralove (Faculty of Science, Department of Chemistry) is looking to appoint a Marie Curie Research Fellow within a fixed term project entitled “Hit selection strategies for identification of kinase inhibitors modulating circadian rhythm in AD”, funded by the Horizon Europe project TClock4AD.
The doctoral candidate will work for two years in Czech Republic (Hradec Kralove University) and for 10 months in Italy (University of Bologna) and will be involved in a 2-month secondment to a Spanish company (Ankar Pharma).
The goals for this DC will be to develop molecules targeting circadian clock and evaluate them in vitro using chemical/biochemical and/or cellular assays. This DC will work in close collaboration with DC1 and DC2 with the aim of optimizing drug candidates directed to particular molecular targets through quantitative mechanistic characterization and preliminary early-ADMET evaluation (including physical-chemical properties, protein binding, serum stability, prediction of BBB permeability, hepato- and neuro-toxicity). The collected data will allow to prioritize different structural classes and rank order them not only based on potency but also in relation to potential downstream absorption, metabolism, or toxicity liabilities. Complementary (bio)pharmaceutical analytical techniques will be exploited for compound profiling, including, but not limited to, surface plasmon resonance for albumin binding assays and liquid chromatography-mass spectrometry for early ADME studies and microsomal assays.
Expected outcomes: The fellow is expected to generate breakthrough ideas in the assigned area of research, as well as to carry out research in line with the project plan. The fellow is also expected to contribute to dissemination and communication activities, besides actively collaborating within the TClock4AD network.
