Thioridazine reverts the phenotype in cellular and Drosophila models of amyotrophic lateral sclerosis by enhancing TDP-43 aggregate clearance

Autor: Lucia Cragnaz, Greta Spinelli, Laura De Conti, Emilie A. Bureau, Janet Brownlees, Fabian Feiguin, Valentina Romano, Natasa Skoko, Raffaella Klima, Catherine A. Kettleborough, Francisco E. Baralle, Marco Baralle

Publikováno v: Neurobiology of Disease, Vol 160, Iss , Pp 105515- (2021)

Brain inclusions mainly composed of misfolded and aggregated TAR DNA binding protein 43 (TDP-43), are characteristic hallmarks of amyotrophic lateral sclerosis (ALS). Irrespective of the role played by the inclusions, their reduction represents an im

Externí odkaz: https://doaj.org/article/4a24bd0945294ac9878244f90dbac4df

N-Hydroxyimides and hydroxypyrimidinones as inhibitors of the DNA repair complex ERCC1–XPF

Autor: Janet Brownlees, David W. Melton, Timothy M. Chapman, Puneet Khurana, Emilie A. Bureau, Simon Fox, Claire Wallace, Preeti Bakrania, P.J. Coombs, Kevin J. Gillen, Barbara Saxty

Publikováno v: Chapman, T M, Wallace, C, Gillen, K J, Bakrania, P, Khurana, P, Coombs, P J, Fox, S, Bureau, E A, Brownlees, J, Melton, D & Saxty, B 2015, ' N-Hydroxyimides and hydroxypyrimidinones as inhibitors of the DNA repair complex ERCC1-XPF ', Bioorganic & Medicinal Chemistry Letters, vol. 25, no. 19 . https://doi.org/doi:10.1016/j.bmcl.2015.08.024

A high throughput screen allowed the identification of N-hydroxyimide inhibitors of ERCC1-XPF endonuclease activity with micromolar potency, but they showed undesirable selectivity profiles against FEN-1. A scaffold hop to a hydroxypyrimidinone templ

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::585f5c51df12368df588aa15c34a6bd8
https://doi.org/10.1016/j.bmcl.2015.08.024

Catechols and 3-hydroxypyridones as inhibitors of the DNA repair complex ERCC1- XPF

Autor: Barbara Saxty, Simon Fox, Timothy M. Chapman, Maximillian T. W. Lee, David W. Melton, Emilie A. Bureau, Preeti Bakrania, Janet Brownlees, Kevin J. Gillen, P.J. Coombs, Claire Wallace, Laura Stennett, Puneet Khurana

Publikováno v: Chapman, T M, Gillen, K J, Wallace, C, Lee, M T, Bakrania, P, Khurana, P, Coombs, P J, Stennett, L, Fox, S, Bureau, E A, Brownlees, J, Melton, D & Saxty, B 2015, ' Catechols and 3-hydroxypyridones as inhibitors of the DNA repair complex ERCC1-XPF ', Bioorganic & Medicinal Chemistry Letters . https://doi.org/doi:10.1016/j.bmcl.2015.08.031

Catechol-based inhibitors of ERCC1-XPF endonuclease activity were identified from a high-throughput screen. Exploration of the structure-activity relationships within this series yielded compound 13, which displayed an ERCC1-XPF IC50 of 0.6 μM, high

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::11a4dad0c8c4ff0e532853e549f314dc
https://www.pure.ed.ac.uk/ws/files/21295310/Chapman_submission_1_main_R1.pdf