Ontology highlight
ABSTRACT:
SUBMITTER: Horton JR
PROVIDER: S-EPMC6467790 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
Horton John R JR Woodcock Clayton B CB Chen Qin Q Liu Xu X Zhang Xing X Shanks John J Rai Ganesha G Mott Bryan T BT Jansen Daniel J DJ Kales Stephen C SC Henderson Mark J MJ Cyr Matthew M Pohida Katherine K Hu Xin X Shah Pranav P Xu Xin X Jadhav Ajit A Maloney David J DJ Hall Matthew D MD Simeonov Anton A Fu Haian H Vertino Paula M PM Cheng Xiaodong X
Journal of medicinal chemistry 20181115 23
The active sites of hundreds of human α-ketoglutarate (αKG) and Fe(II)-dependent dioxygenases are exceedingly well preserved, which challenges the design of selective inhibitors. We identified a noncatalytic cysteine (Cys481 in KDM5A) near the active sites of KDM5 histone H3 lysine 4 demethylases, which is absent in other histone demethylase families, that could be explored for interaction with the cysteine-reactive electrophile acrylamide. We synthesized analogs of a thienopyridine-based inhibi ...[more]