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Residence Time, a New parameter to Predict Neurosteroidogenic Efficacy of Translocator Protein (TSPO) Ligands: the Case Study of N , N ‐Dialkyl‐2‐arylindol‐3‐ylglyoxylamides
Author(s) -
Costa Barbara,
Taliani Sabrina,
Da Pozzo Eleonora,
Barresi Elisabetta,
Robello Marco,
Cavallini Chiara,
Cosconati Sandro,
Da Settimo Federico,
Novellino Ettore,
Martini Claudia
Publication year - 2017
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700220
Subject(s) - translocator protein , in vitro , ligand (biochemistry) , drug discovery , computational biology , chemistry , pharmacology , plasma protein binding , drug development , biochemistry , drug , biology , receptor , immunology , inflammation , neuroinflammation
Targeting the biosynthetic pathway of neuroactive steroids with specific 18 kDa translocator protein (TSPO) ligands may be a viable therapeutic approach for a variety of neurodegenerative and neuropsychiatric diseases. However, the lack of correlation between binding affinity and in vitro steroidogenic efficacy has limited the identification of lead compounds by traditional affinity‐based drug discovery strategies. Our recent research indicates that the key factor for robust steroidogenic TSPO ligand efficacy is not the binding affinity per se, but rather the time the compound spends in 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.