Antje Dittmann

TL;DR: It is shown that a novel small molecule inhibitor of the BET family, GSK1210151A (I-BET151), has profound efficacy against human and murine MLL-fusion leukaemic cell lines, through the induction of early cell cycle arrest and apoptosis, establishing the displacement of BET proteins from chromatin as a promising epigenetic therapy for these aggressive leukaemias.

TL;DR: This work revealed the selectivity with which 16 HDAC inhibitors target multiple HDAC complexes scaffolded by ELM-SANT domain subunits, including a novel mitotic deacetylase complex (MiDAC) and identified several non-HDAC targets for hydroxamate inhibitors.

TL;DR: I-BRD9 represents the first selective tool compound available to elucidate the cellular phenotype of BRD9 bromodomain inhibition, leading to greater than 700-fold selectivity over the BET family and 200-fold over the highly homologous bromidomain-containing protein 7 (BRD7).

TL;DR: It is demonstrated that a common ‘core’ transcriptional program, which is HOX gene independent, is downregulated in AML and underlies sensitivity to I-BET treatment, and this program can independently classify AML patients into distinct cytogenetic and molecular subgroups, suggesting that it contains biomarkers of sensitivity and response.

TL;DR: The optimization of the kinobead assay is reported resulting in the combination of five chemical probes and four cell lines to cover half the human kinome in a single assay (∼ 260 kinases).