TY - JOUR T1 - Computational evidence of a compound with nicotinic α4β2-Ach receptor partial agonist properties as possible coadjuvant for the treatment of obesity JF - bioRxiv DO - 10.1101/088138 SP - 088138 AU - Helena den-Haan AU - Juan José Hernández Morante AU - Horacio Pérez-Sánchez Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/11/16/088138.abstract N2 - Background Nowadays, the search for new anti-obesity drugs is oriented to the use of anti-addiction medications like bupropion and naltrexone. Other compounds like varenicline may be also useful to treat obesity. However, the low effectiveness of the former or the high number of adverse effects of the latter makes it necessary to search for new therapeutic agents.Methods Screening database selected for the computational experiments was DrugBank. 3D global shape comparison with varenicline was performed by means of the Ligand Based Virtual Screening tool WEGA v2015. A pharmacophore model based in the structure of varenicline was created by means of LigandScout v4.08. The in-silico screening was performed using Relative Pharmacophore Fit (RPF) scoring function implemented in LigandScout. Up to 3 mismatches with varenicline pharmacophore model were allowed for hits retrieving.Results Drugbank database was screened in silico to find alternative molecules to varenicline, and the compound cevimeline was found to have strong similarity to varenicline in terms of 3D shape and pharmacophoric features. Thus, we propose this hit may interact with nicotinic α4β2-Ach receptor in the same mode as varenicline does.Discussion The functional activities of this compound and its validity as a drug therapy for obesity treatment must be confirmed in further in vitro, in vivo and preclinical studies; however, attending to our screening procedure, this compound should be a promising therapy for such a complex disorder such as obesity. ER -