43 research outputs found
sc-PDB: a database for identifying variations and multiplicity of 'druggable' binding sites in proteins
Incidence, nature, severity, and causes of dispensing errors in community pharmacies in Jordan
Computational Profiling of Bioactive Compounds Using a Target-Dependent Composite Workflow
Investigating prescribing errors in the emergency department of a large governmental hospital in Jordan
Comparison of structures and cytotoxicity of mupirocin and batumin against melanoma and several other cancer cell lines
Structure–Activity Relationship Studies for Enhancer of Zeste Homologue 2 (EZH2) and Enhancer of Zeste Homologue 1 (EZH1) Inhibitors
EZH2
or EZH1 (enhancer of zeste homologue 2 or 1) is the catalytic
subunit of polycomb repressive complex 2 (PRC2) that catalyzes methylation
of histone H3 lysine 27 (H3K27). PRC2 hyperactivity and/or hypertrimethylation
of H3K27 are associated with numerous human cancers, therefore inhibition
of PRC2 complex has emerged as a promising therapeutic approach. Recent
studies have shown that EZH2 and EZH1 are not functionally redundant
and inhibition of both EZH2 and EZH1 is necessary to block the progression
of certain cancers such as mixed-lineage leukemia (MLL)-rearranged
leukemias. Despite the significant advances in discovery of EZH2 inhibitors,
there has not been a systematic structure–activity relationship
(SAR) study to investigate the selectivity between EZH2 and EZH1 inhibition.
Here, we report our SAR studies that focus on modifications to various
regions of the EZH2/1 inhibitor UNC1999 (<b>5</b>) to investigate
the impact of the structural changes on EZH2 and EZH1 inhibition and
selectivity