Targeting neuroactive steroid biosynthetic pathway by specific 18 kDa Translocator Protein (TSPO) ligands may represent a therapeutic approach in a variety of neurodegenerative and neuropsychiatric diseases. However, the lack of correlation between the binding affinity and the in vitro steroidogenic efficacy has limited the identification of lead compounds by a traditional affinity-based drug discovery strategy. Our recent researches indicate that the key factor for robust steroidogenic TSPO ligand efficacy is not the binding affinity per se, but rather the time the compound spends into the target, namely its Residence Time (RT). The assessment of this kinetic parameter during the in vitro characterization of compounds appears mandatory in order to obtain structure-efficacy relationships suitable for the future development of novel molecules with promising pharmacological properties.
Residence Time (RT), a new parameter to predict neurosteroidogenic efficacy of Translocator Protein (TSPO) ligands: N,N-dialkyl-2-arylindol-3-ylglyoxylamides, a case study
TALIANI, SABRINA
Secondo
;COSTA, BARBARAPrimo
;DA POZZO, ELEONORA;BARRESI, ELISABETTA;ROBELLO, MARCO;CAVALLINI, CHIARA;DA SETTIMO PASSETTI, FEDERICO;MARTINI, CLAUDIAUltimo
2017-01-01
Abstract
Targeting neuroactive steroid biosynthetic pathway by specific 18 kDa Translocator Protein (TSPO) ligands may represent a therapeutic approach in a variety of neurodegenerative and neuropsychiatric diseases. However, the lack of correlation between the binding affinity and the in vitro steroidogenic efficacy has limited the identification of lead compounds by a traditional affinity-based drug discovery strategy. Our recent researches indicate that the key factor for robust steroidogenic TSPO ligand efficacy is not the binding affinity per se, but rather the time the compound spends into the target, namely its Residence Time (RT). The assessment of this kinetic parameter during the in vitro characterization of compounds appears mandatory in order to obtain structure-efficacy relationships suitable for the future development of novel molecules with promising pharmacological properties.File | Dimensione | Formato | |
---|---|---|---|
2017_ChemMedChem_concept.pdf
solo utenti autorizzati
Descrizione: Articolo principale
Tipologia:
Versione finale editoriale
Licenza:
NON PUBBLICO - Accesso privato/ristretto
Dimensione
2.13 MB
Formato
Adobe PDF
|
2.13 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
2017_ChemMedChem_concept_accepted manuscript.pdf
accesso aperto
Descrizione: Articolo principale
Tipologia:
Documento in Post-print
Licenza:
Creative commons
Dimensione
655.05 kB
Formato
Adobe PDF
|
655.05 kB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.