Author:
Stefan Sven Marcel,Pahnke Jens,Namasivayam Vigneshwaran
Abstract
AbstractThe discovery of both distinctive lead molecules and novel drug targets is a great challenge in drug discovery, which particularly accounts for orphan diseases. Huntington’s disease (HD) is an orphan, neurodegenerative disease of which the pathology is well-described. However, its pathophysiological background and molecular mechanisms are poorly understood. To date, only 2 drugs have been approved on the US and European markets, both of which address symptomatic aspects of this disease only. Although several hundreds of agents were described with efficacy against the HD phenotype in in vitro and/or in vivo models, a successful translation into clinical use is rarely achieved. Two major impediments are, first, the lack of awareness and understanding of the interactome—the sum of key proteins, cascades, and mediators—that contributes to HD initiation and progression; and second, the translation of the little gained knowledge into useful model systems. To counteract this lack of data awareness, we manually compiled and curated the entire modulator landscape of successfully evaluated pre-clinical small-molecule HD-targeting agents which are annotated with substructural molecular patterns, physicochemical properties, as well as drug targets, and which were linked to benchmark databases such as PubChem, ChEMBL, or UniProt. Particularly, the annotation with substructural molecular patterns expressed as binary code allowed for the generation of target-specific and -unspecific fingerprints which could be used to determine the (poly)pharmacological profile of molecular-structurally distinct molecules.
Funder
Deutsche Forschungsgemeinschaft
Aufzien Family Center for the Prevention and Treatment of Parkinson’s Disease , Nasjonalforeningen
HelseSØ
Barnekreftforeningen
EEA Grants/Norway Grants
Norges Forskningsråd
Rheinische Friedrich-Wilhelms-Universität Bonn
Publisher
Springer Science and Business Media LLC
Subject
Library and Information Sciences,Computer Graphics and Computer-Aided Design,Physical and Theoretical Chemistry,Computer Science Applications
Cited by
2 articles.
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