ArticleACS medicinal chemistry letters2022
Identification of a BAZ2A-Bromodomain Hit Compound by Fragment Growing.
Article in ACS medicinal chemistry letters, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Unusual backfolded binding poses of BAZ2A bromodomain binders.Acta crystallographica. Section D, Structural biology · 2026Article
- Recent Progress and Prospect in Studying Selective Inhibitors Toward Bromodomain Family Members.Molecules (Basel, Switzerland) · 2026Review
- Increasing the Accuracy and Robustness of the CHARMM General Force Field with an Expanded Training Set.Journal of chemical theory and computation · 2025Article
- Discovery of First-in-Class BAZ2A/B and BAZ2B-Selective Degraders.ACS medicinal chemistry letters · 2025Article
- Enhanced cellular death in liver and breast cancer cells by dual BET/BRPF1 inhibitors.Protein science : a publication of the Protein Society · 2024Article
- Reevaluation of bromodomain ligands targeting BAZ2A.Protein science : a publication of the Protein Society · 2023Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BAZ2A is an epigenetic regulator affecting transcription of ribosomal RNA. It is overexpressed in aggressive and recurrent prostate cancer, promoting cellular migration. Its bromodomain is characterized by a shallow and difficult-to-drug pocket. Here, we describe a structure-based fragment-growing campaign for the identification of ligands of the BAZ2A bromodomain. By combining docking, competition binding assays, and protein crystallography, we have extensively explored the interactions of the ligands with the rim of the binding pocket, and in particular ionic interactions with the side chain of Glu1820, which is unique to BAZ2A. We present 23 high-resolution crystal structures of the holo BAZ2A bromodomain and analyze common bromodomain/ligand motifs and favorable intraligand interactions. Binding of some of the compounds is enantiospecific, with affinity in the low micromolar range. The most potent ligand has an equilibrium dissociation constant of 7 μM and a good selectivity over the paralog BAZ2B bromodomain.
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Registered trials
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