title: Novel scaffolds for modulation of TRPV1 identified with pharmacophore modeling and virtual screening.
abstract: OBJECTIVE
  The transient receptor potential vanilloid type 1 (TRPV1) is responsible for pain perception in the peripheral nervous system (PNS). TRPV1 is thus considered a versatile target for development of non-opioid analgesics.
  
  
  RESULTS
  Pharmacophore-based clustering of a publicly available data set of TRPV1 antagonists revealed a set of models, which were validated with data sets of inactive compounds, decoys and known drug candidates. The top ranked pharmacophore models were subsequently used for virtual screening. Based on a unique in-house protocol, a set of compounds was selected and biologically tested for modulation of TRPV1 in a voltage-clamp model.
  
  
  CONCLUSIONS
  Pharmacophore models extracted from large public data sets are a valuable source for identification of novel scaffolds for TRPV1 receptor modulation.
authors.affiliation: University of Vienna, Department of Pharmaceutical Chemistry, Althanstrasse 14, 1090 Vienna, Austria.
authors.forename: Daria
authors.initials: D
authors.lastname: Goldmann
authors.forename: Peter
authors.initials: P
authors.lastname: Pakfeifer
authors.forename: Steffen
authors.initials: S
authors.lastname: Hering
authors.forename: Gerhard F
authors.initials: GF
authors.lastname: Ecker
mesh_terms: D000465:Algorithms; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D017933:Peripheral Nervous System / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D018712:Analgesics, Non-Narcotic; D008024:Ligands; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human
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