Ontology highlight
ABSTRACT:
SUBMITTER: Scheufler C
PROVIDER: S-EPMC4983739 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
Scheufler Clemens C Möbitz Henrik H Gaul Christoph C Ragot Christian C Be Céline C Fernández César C Beyer Kim S KS Tiedt Ralph R Stauffer Frédéric F
ACS medicinal chemistry letters 20160606 8
Mixed lineage leukemia (MLL) gene rearrangement induces leukemic transformation by ectopic recruitment of disruptor of telomeric silencing 1-like protein (DOT1L), a lysine histone methyltransferase, leading to local hypermethylation of H3K79 and misexpression of genes (including HoxA), which drive the leukemic phenotype. A weak fragment-based screening hit identified by SPR was cocrystallized with DOT1L and optimized using structure-based ligand optimization to yield compound 8 (IC50 = 14 nM). T ...[more]