Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00584 - e00584
Published: April 1, 2025
Language: Английский
Molecules, Journal Year: 2025, Volume and Issue: 30(5), P. 990 - 990
Published: Feb. 21, 2025
Dual specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A), a phosphorylation kinase, is localized within the central nervous system and linked to hyperphosphorylation of Tau. Imaging DYRK1A may provide an earlier biomarker for Tauopathies, including Alzheimer’s disease (AD). We have used Chimera-Autodock evaluate potential molecules binding site DYRK1A. Five molecules, 10-bromo-2-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acid (4E3), 10-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic (KuFal184), harmine, 6-(fluoro-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine (MK-6240), 6-iodo-3-(1H-pyrrolo[2,3-c]pyridine-1-yl)isoquinoline (IPPI), were found energies −10.4, −10.1, −9.0, −9.1, −9.4 kcal/mole, respectively. Two 4E3 KuFal184, selective DYRK1A, while harmine also had monoamine oxidase A affinity, MK-6240 IPPI affinity Tau present in brain slices AD subject labeled with [125I]IPPI. KuFal184 no effect on [125I]IPPI, suggesting absence overlap two molecules. MK-6240, known agent was, however, able compete The suggest affinities approximately 80–100 nM, which insufficient serve as imaging agent. higher (6 nM DYRK1A) suggested that [125I]KuFal184 be Electrophilic radioiodination was synthesize modest yields (25%) high radiochemical purity (>95%). Preliminary studies showed some selectivity cortical grey matter regions containing
Language: Английский
Citations
0
Current Alzheimer Research, Journal Year: 2025, Volume and Issue: 21(10), P. 691 - 692
Published: March 1, 2025
Language: Английский
Citations
0
Neurotherapeutics, Journal Year: 2025, Volume and Issue: unknown, P. e00584 - e00584
Published: April 1, 2025
Language: Английский
Citations
0