title: Novel virtual screening approach for the discovery of human tyrosinase inhibitors.
abstract: Tyrosinase is the key enzyme involved in the human pigmentation process, as well as the undesired browning of fruits and vegetables. Compounds inhibiting tyrosinase catalytic activity are an important class of cosmetic and dermatological agents which show high potential as depigmentation agents used for skin lightening. The multi-step protocol employed for the identification of novel tyrosinase inhibitors incorporated the Shape Signatures computational algorithm for rapid screening of chemical libraries. This algorithm converts the size and shape of a molecule, as well its surface charge distribution and other bio-relevant properties, into compact histograms (signatures) that lend themselves to rapid comparison between molecules. Shape Signatures excels at scaffold hopping across different chemical families, which enables identification of new actives whose molecular structure is distinct from other known actives. Using this approach, we identified a novel class of depigmentation agents that demonstrated promise for skin lightening product development.
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, P.R. China.
authors.forename: Ni
authors.initials: N
authors.lastname: Ai
authors.affiliation: Department of Pharmacology, Robert Wood Johnson Medical School, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: William J
authors.initials: WJ
authors.lastname: Welsh
authors.affiliation: Global R&D, AVON Products, Inc., Suffern, New York, United States of America.
authors.forename: Uma
authors.initials: U
authors.lastname: Santhanam
authors.affiliation: Global R&D, AVON Products, Inc., Suffern, New York, United States of America.
authors.forename: Hong
authors.initials: H
authors.lastname: Hu
authors.affiliation: Global R&D, AVON Products, Inc., Suffern, New York, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Lyga
mesh_terms: D000363:Agaricales / Q000737:chemistry / Q000201:enzymology; D000465:Algorithms; D000818:Animals; D045744:Cell Line, Tumor; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D057166:High-Throughput Screening Assays; D006801:Humans; D008546:Melanoma, Experimental / Q000201:enzymology / Q000473:pathology; D051379:Mice; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010858:Pigmentation / Q000187:drug effects*; D011753:Pyrones / Q000494:pharmacology; D012867:Skin / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D062327:Skin Lightening Preparations / Q000737:chemistry* / Q000494:pharmacology; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology; D055672:Static Electricity; D013329:Structure-Activity Relationship; D014584:User-Computer Interface
chemical_list: D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D011753:Pyrones; D062327:Skin Lightening Preparations; D054852:Small Molecule Libraries; C011890:kojic acid; D014442:Monophenol Monooxygenase