Imaging Mutant Huntingtin Aggregates: Development of a Potential PET Ligand.
Animals
Disease Models, Animal
Dogs
Female
Humans
Huntingtin Protein
/ analysis
Huntington Disease
/ diagnostic imaging
Ligands
Madin Darby Canine Kidney Cells
Male
Mice
Mice, Inbred C57BL
Mutation
Peptides
/ genetics
Positron-Emission Tomography
/ methods
Protein Aggregation, Pathological
/ diagnostic imaging
Radiopharmaceuticals
/ analysis
Rats, Sprague-Dawley
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
13 08 2020
13 08 2020
Historique:
pubmed:
15
7
2020
medline:
15
12
2020
entrez:
15
7
2020
Statut:
ppublish
Résumé
Mutant huntingtin (mHTT) protein carrying the elongated N-terminal polyglutamine (polyQ) tract misfolds and forms protein aggregates characteristic of Huntington's disease (HD) pathology. A high-affinity ligand specific for mHTT aggregates could serve as a positron emission tomography (PET) imaging biomarker for HD therapeutic development and disease progression. To identify such compounds with binding affinity for polyQ aggregates, we embarked on systematic structural activity studies; lead optimization of aggregate-binding affinity, unbound fractions in brain, permeability, and low efflux culminated in the discovery of compound
Identifiants
pubmed: 32662649
doi: 10.1021/acs.jmedchem.0c00955
doi:
Substances chimiques
HTT protein, human
0
Htt protein, mouse
0
Huntingtin Protein
0
Ligands
0
Peptides
0
Radiopharmaceuticals
0
polyglutamine
26700-71-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM