Novel scaffolds for modulation of TRPV1 identified with pharmacophore modeling and virtual screening

Authors/others:Goldmann, Daria; Pakfeifer, Peter; Hering, Steffen; Ecker, Gerhard F
Abstract:

AIM: 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.

CONCLUSION: Pharmacophore models extracted from large public data sets are a valuable source for identification of novel scaffolds for TRPV1 receptor modulation.

Language:English
Number of pages:14
Date of publication:2015
Journal title:Future Medicinal Chemistry
Volume:7
Number:3
Pages:243-56
Peer reviewed:true
Links:
Digital Object Identifier (DOI):http://dx.doi.org/10.4155/fmc.14.168
Publication Type:Article
Portal:https://ucris.univie.ac.at/portal/en/publications/novel-scaffolds-for-modulation-of-trpv1-identified-with-pharmacophore-modeling-and-virtual-screening(0149bb72-249e-44ed-a2ce-0ce1c9bbcc58).html