Within the ICB, the expertise needed to cover from hit (small molecules, peptido or glycomimetics, modified DNA/RNAs) to lead candidate will be reinforced. We are establishing cutting-edge biophysical, enzymatic, structural, cellular and phenotypic assays, leveraging a wide array of technologies. This innovation combined to in-house or national chemical libraries[i] and the HCS[ii] and HTS[iii] capacity, in addition to virtual screening and AI-based approaches,[iv] will provide original hits. Rounds of medicinal chemistry,[v] orthogonal/secondary functional assays together with target engagement, chemoproteomics, in silico[vi] and experimental ADMET optimisation, formulation[vii] and preclinical studies will deliver lead compounds. The technological platforms will be a major asset.[viii] Infectious diseases, inflammation, cancer and neurodegenerative diseases will be the main targets. Discoveries of new therapies via this innovative infrastructure will nurture the emergence of startups and companies.
[i] https://chembiofrance.cn.cnrs.fr/en/composante/chimiotheque
[ii] Boulle,M. et al, Cells. 2022;11(23) (https://doi.org/10.3390/cells11233862).
[iii] Yang L. et al, Angew Chem Int Ed Engl. 2024;63(3):e202314587 (https://doi.org/10.1002/anie.202314587)
[iv] Dudas, B. et al, iScience 2022, 25, 105290 (https://doi.org/10.1016/j.isci.2022.105290)
[v] a) Liu, WQ. et al, Cancer Lett. 2018, 414, 88-98 (https://doi.org/10.1016/j.canlet.2017.10.039); b) Laaroussi, H. et al, Eur. J. Med. Chem. 2020, 202, 112561 (https://doi.org/10.1016/j.ejmech.2020.112561): c) Fichez, J. et al, RSC Med. Chem. 2020, 11, 577-582 (https://doi.org/10.1039/D0MD00025F); d) Nardella, F. et al, J. Med. Chem. 2021, 64, 10403-10417 (https://doi.org/10.1021/acs.jmedchem.1c00821)
[vi] Dudas, B. et al, Trends Pharmacol Sci. 2024, 45, 39-55 (https://doi.org/10.1016/j.tips.2023.11.001)
[viii] The consortium offers unique technological platforms in CryoEM/crystallography, protein/antibody purification, NMR, MS, biophysics, dynamic imaging, metabolism profiling, and molecular modelling