Natural and synthetic inhibitors of FGF-dependent angiogenesis for tumor targeted therapies (DCM.AD007.151)

Area tematica

Scienze chimiche e tecnologie dei materiali

Area progettuale

Struttura responsabile del progetto di ricerca

Istituto di Scienze e Tecnologie Chimiche "Giulio Natta" (SCITEC)

Responsabile di progetto

LAURAGIUDITTA RAGONA
Telefono: 0223699619
E-mail: laura.ragona@scitec.cnr.it

Abstract

Fibroblast growth factor (FGF)/Fibroblast growth factor Receptor (FGFR) signalling pathways regulate cell proliferation, angiogenesis and are recognized therapeutic targets for a wide array of pathologies, including angiogenesis-driven diseases and cancer.
To date, several FGFR specific inhibitors have been developed (TKI inhibitors, antibodies and extracellular allosteric inhibitors of FGFR). A drug design approach, combining MD, NMR and biological data, allowed us to design and select small molecules, mimicking the function of the endogenous protein inhibitors thrombospondin-1 and pentraxin-3. These molecules specifically targeted FGF2 with effects on the stability of the whole FGF2/FGFR/HSPG ternary complex (Foglieni et al, 2016; Pagano et al, 2012) and showed anti-cancer efficiency in vitro and in vivo. We recently investigated the ability of natural products to target the FGF/FGFR system. A detailed molecular level description can be derived by NMR and docking studies. Cellular studies on FGF2-induced endothelial cells proliferation and FGFR phosphorylation complement the spectroscopic results and validate the proposed mechanism of antiangiogenic action.

Obiettivi

Identification of antiangiogenic molecules
Description of the molecular mechanism of action
Design of new synthetic inhibitors

Data inizio attività

01/07/2020

Parole chiave

NMR, angiogenesis, drug discovery

Ultimo aggiornamento: 20/05/2024