FKBP5 blockade may provide a new horizon for the treatment of stress‐associated disorders: An in‐silico study

Abstract

AbstractObjectiveWe searched for, from the FDA (Food and Drug Administration‐USA)‐approved drugs, inhibitors of FKBP5 with tolerable adverse effect profiles (eg, mild headache, sedation, etc.) and with the ability to cross the blood brain barrier (BBB), using bio‐informatics tools (in‐silico). This may pave the road for designing clinical trials of such drugs in patients with functional seizures (FS) and other stress‐associated disorders.MethodsSeveral databases were used to find all the approved drugs that potentially have interactions with FKBP51 protein [ie, CTD gene‐chemical interaction section of FKBP51 protein of Harmonizome of Mayaanlab, DrugCenteral database, PDID (Protein Drug Interaction Database), DGIdb (the Drug Gene Interaction database)]. Other databases were also searched [eg, clinicaltrials.gov; DRUGBANK (the FASTA format of the FKBP51 protein was imported to the target sequencing section of the database to find the associated drugs), and the STITCH database (to find the related chemical interaction molecules)].ResultsAfter a comprehensive search of the designated databases, 28 unique and approved drugs were identified. Fluticasone propionate and Mifepristone and Ponatinib, Mirtazapine, Clozapine, Enzalutamide, Sertraline, Prednisolone, Fluoxetine, Dexamethasone, Clomipramine, Duloxetine, Citalopram, Chlorpromazine, Nefazodone, and Escitalopram are inhibitors of FKBP5 and have BBB permeability.SignificanceWhile the current in‐silico repurposing study could identify potential drugs (that are already approved and are widely available) for designing clinical trials in patients with stress‐associated disorders (eg, FS), any future clinical trial should consider the pharmacological profile of the desired drug and also the characteristics and comorbidities of the patients in order to foster a success.