title: [Selection of a melanine concentrating hormone receptor-1 (MCHR1) antagonists' focused library and its biological screening with AequoScreen].
abstract: Target focused libraries can be rapidly selected by 2D virtual screening methods from multimillion compounds' repositories if structures of active compounds are available. In the present study a multi-step virtual and in vitro screening cascade is reported to select Melanin Concentrating Hormone Receptor-1 (MCHR1) antagonists. The 2D similarity search combined with physicochemical parameter filtering is suitable for selecting candidates from multimillion compounds' repository. The seeds of the first round virtual screening were collected from the literature and commercial databases, while the seeds of the second round were the hits of the first round. In vitro screening underlined the efficiency of our approach, as in the second screening round the hit rate (8.6 %) significantly improved compared to the first round (1.9%), reaching the antagonist activity even below 10 nM.
authors.affiliation: TargetEx, H-2120 Kápolna köz 4/a, Dunakeszi, Hungary.
authors.forename: Beáta
authors.initials: B
authors.lastname: Flachner
authors.affiliation: TargetEx, H-2120 Kápolna köz 4/a, Dunakeszi, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Hajdú
authors.affiliation: TargetEx, H-2120 Kápolna köz 4/a, Dunakeszi, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Dobi
authors.affiliation: TargetEx, H-2120 Kápolna köz 4/a, Dunakeszi, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Lorincz
authors.affiliation: TargetEx, H-2120 Kápolna köz 4/a, Dunakeszi, Hungary.
authors.forename: Sándor
authors.initials: S
authors.lastname: Cseh
authors.affiliation: TargetEx, H-2120 Kápolna köz 4/a, Dunakeszi, Hungary.
authors.forename: György
authors.initials: G
authors.lastname: Dormán
mesh_terms: D000331:Aequorin / Q000032:analysis / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003514:Cyclohexylamines / Q000737:chemistry; D062126:Databases, Chemical; D062313:Databases, Pharmaceutical; D015195:Drug Design; D055808:Drug Discovery; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008027:Light; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry; D011799:Quinazolines / Q000737:chemistry; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D014584:User-Computer Interface
chemical_list: D003514:Cyclohexylamines; C103263:MCHR1 protein, human; C519479:N-(3-(1-((4-(3,4-difluorophenoxy)phenyl)methyl)(4-piperidyl))-4-methylphenyl)-2-methylpropanamide; C501654:N-(4-((4-(dimethylamino)quinazolin-2-yl)amino)cyclohexyl)-3,4-difluorobenzamide; D010880:Piperidines; D011799:Quinazolines; D017481:Receptors, Somatostatin; D000331:Aequorin