Affinage

BRD9

Bromodomain-containing protein 9 · UniProt Q9H8M2

Length
597 aa
Mass
67.0 kDa
Annotated
2026-04-28
91 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BRD9 is the defining bromodomain-containing subunit of the non-canonical BAF (ncBAF/GBAF) chromatin remodeling complex, where it functions as a multivalent epigenetic reader that recruits SWI/SNF remodeling activity to specific genomic loci in a context-dependent manner to regulate gene expression programs governing pluripotency, hematopoiesis, immune signaling, DNA repair, and metabolism. Its bromodomain reads acetylated lysines on histones (H3K27ac, H3K18ac) and non-histone proteins (RAD54 K515ac, CCAR2), and also recognizes methylated arginine (AKT1 R391me) and lactylated lysine (H3K18la), while its DUF3512 domain is essential for ncBAF complex integrity (PMID:30510198, PMID:31015438, PMID:32457312, PMID:40279411, PMID:41792243). BRD9 physically interacts with BRD4 and BRD2 to coordinate BET-SWI/SNF cooperation at promoters and enhancers, and partners with transcription factors including CTCF, androgen receptor, GR, SMAD2/3, FOXP1, RELA, PPARα, and p53 to direct locus-specific chromatin accessibility and transcriptional output (PMID:33355184, PMID:34983841, PMID:34446564, PMID:36918560, PMID:37870468, PMID:40780491, PMID:40613709). BRD9 loss increases CTCF chromatin occupancy and alters three-dimensional chromatin architecture within topologically associating domains, and disrupts R-loop resolution at transcription-replication conflict sites, linking its function to genome stability and myeloid differentiation (PMID:38102116, PMID:40613709, PMID:41219678).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2015 High

    Establishing that BRD9 contains a druggable acetyl-lysine-reading bromodomain with unique structural plasticity resolved whether this domain could be selectively targeted apart from the closely related BRD7 and BET family members.

    Evidence Crystal structures of BRD9 bromodomain with ligands revealed an induced-fit rearrangement of the acetyl-lysine pocket, and I-BRD9 achieved >700-fold selectivity over BET and >200-fold over BRD7, displacing BRD9 from chromatin in Kasumi-1 AML cells

    PMID:25703523 PMID:25856009

    Open questions at the time
    • No histone mark specificity defined at this stage
    • Cellular targets of BRD9 bromodomain beyond generic chromatin association unknown
  2. 2016 High

    Demonstrating that BRD9's bromodomain engagement sustains MYC transcription in AML cells established the first functional requirement for BRD9 reader activity in an oncogenic transcriptional program.

    Evidence Bromodomain-swap resistance allele in AML cells confirmed that antiproliferative effects of BRD9 inhibitors are on-target and linked to MYC transcript downregulation

    PMID:27376689

    Open questions at the time
    • Which SWI/SNF sub-complex BRD9 belongs to was not yet defined
    • Mechanism by which BRD9 is recruited to MYC locus not resolved
  3. 2018 High

    Identifying BRD9 as the defining subunit of a non-canonical BAF complex (ncBAF/GBAF) containing GLTSCR1/GLTSCR1L resolved the composition of a previously uncharacterized SWI/SNF variant and revealed its BRD4-dependent chromatin recruitment at naive pluripotency loci.

    Evidence Reciprocal Co-IP, ChIP-seq, and bromodomain inhibitor treatments in mouse ESCs showed GBAF is distinct from esBAF; BRD9 interacts with BRD4 in a bromodomain-dependent manner

    PMID:30510198

    Open questions at the time
    • Whether BRD9-BRD4 interaction is direct or mediated through shared chromatin marks
    • Structural basis of GLTSCR1 incorporation into ncBAF
  4. 2019 High

    Establishing that the DUF3512 domain (not the bromodomain) is essential for SWI/SNF complex integrity in SMARCB1-mutant cancers revealed a synthetic lethal vulnerability and separated BRD9's scaffolding from its reader function.

    Evidence CRISPR screen and domain deletion analysis in rhabdoid tumor cells showed SMARCB1 loss increases BRD9 incorporation and creates BRD9 dependency through DUF3512

    PMID:31015438

    Open questions at the time
    • Structural basis of DUF3512-mediated complex assembly unknown
    • Whether DUF3512 dependency extends to other SMARCB1-deficient tumor types
  5. 2019 Medium

    Demonstrating BRD9 as an acetyl-reader of non-histone substrates (CCAR2) broadened its recognition repertoire beyond histone tails and implicated it in Wnt coactivator regulation.

    Evidence Protein domain arrays and pull-down assays showed BRD9 bromodomain binds acetylated CCAR2, contributing to a BET/BRD9 acetyl switch in colorectal cancer

    PMID:30643017

    Open questions at the time
    • Direct binding affinity not quantified
    • Specificity of BRD9 versus BET recognition of CCAR2 acetylation unclear
  6. 2020 High

    Identifying BRD9 as a reader of acetylated RAD54 that facilitates RAD54-RAD51 interaction established a direct role for BRD9 in homologous recombination DNA repair, independent of its canonical chromatin remodeling function.

    Evidence Co-IP, pulldown, and HR reporter assays showed BRD9 bromodomain binds RAD54 K515ac and is required for RAD54-RAD51 complex formation after DNA damage

    PMID:32457312

    Open questions at the time
    • Whether BRD9-RAD54 interaction occurs in the context of ncBAF or as a free subunit
    • No structural model of BRD9-RAD54 interaction
  7. 2020 High

    Showing that BRD9/ncBAF interacts with androgen receptor and CTCF and co-localizes with BET proteins genome-wide in prostate cancer linked ncBAF to steroid hormone-driven transcription.

    Evidence Co-IP of BRD9 with AR and CTCF, ChIP-seq overlap with BET, and BRD9 degrader/inhibitor treatment reducing AR target gene expression and xenograft tumor growth

    PMID:33355184

    Open questions at the time
    • Whether BRD9 directly bridges AR and BRD4 or they are independently recruited
    • Contribution of CTCF to BRD9-AR cooperation not dissected
  8. 2021 High

    Demonstrating that BRD9 depletion enhances GR occupancy at inflammatory gene loci established BRD9 as a genomic antagonist of glucocorticoid receptor, revealing a competition model for transcription factor access at shared sites.

    Evidence ChIP-seq with BRD9 inhibition/degradation/knockout in macrophages showed increased GR binding at inflammatory genes; validated in vivo in high-fat diet mouse model

    PMID:34446564

    Open questions at the time
    • Whether BRD9-GR antagonism is direct or mediated through chromatin state changes
    • Mechanism by which ncBAF limits GR accessibility not resolved
  9. 2022 High

    Establishing that BRD9 and BRD4 are co-recruited to ISG promoters with ISGF3 upon endotoxin stimulation, and that BRD9 loss reduces STAT1/2/IRF9 binding, defined BRD9 as a chromatin prerequisite for interferon-stimulated gene activation in innate immunity.

    Evidence ChIP-seq in macrophages with BRD9 inhibitor and dBRD9 degrader showed diminished ISGF3 component occupancy at ISG loci; complemented by truncation variants failing to rescue IFN responses

    PMID:34983841 PMID:36100643

    Open questions at the time
    • Whether BRD9 directly recruits ISGF3 or remodels chromatin to permit ISGF3 binding
    • Contribution of ncBAF ATPase activity versus BRD9 reader activity not separated
  10. 2023 Medium

    Identifying BRD9 in a complex with SMAD2/3, BRD4, β-catenin, and P300 at pluripotency genes, and showing BRD9 mediates enhancer-promoter looping for stemness genes, unified its roles in TGF-β/Wnt signaling and 3D chromatin architecture.

    Evidence Co-IP of multi-protein complex in hESCs, ChIP-seq for H3K27ac, rescue with pathway ligands; chromatin looping analysis in pancreatic cancer stem cells

    PMID:37739089 PMID:37870468

    Open questions at the time
    • Stoichiometry of the BRD9-SMAD2/3-BRD4-P300 complex not defined
    • Whether BRD9 directly mediates looping or acts indirectly through cohesin/CTCF
  11. 2023 High

    Demonstrating that BRD9 loss in hematopoietic stem cells increases CTCF chromatin occupancy and alters chromatin architecture within TADs revealed BRD9 as a modulator of 3D genome organization controlling myeloid differentiation.

    Evidence Multi-omics (ChIP-seq, ATAC-seq, Hi-C, RNA-seq) in conditional Brd9 knockout mice showed enhanced CTCF binding and myeloid gene activation

    PMID:38102116

    Open questions at the time
    • How ncBAF mechanistically limits CTCF occupancy (direct competition vs. nucleosome positioning)
    • Whether altered TAD structure is a cause or consequence of differentiation changes
  12. 2025 High

    Discovering that BRD9 reads methylated arginine on AKT1 (R391me) through an aromatic cage in its bromodomain fundamentally expanded the recognition code beyond acetyl-lysine to include arginine methylation marks.

    Evidence Biochemical binding assays and aromatic cage mutagenesis showed direct BRD9 bromodomain binding to AKT1 R391me; functional cooperation with EZH2-mediated H3K27me shown by synergy assays

    PMID:40279411

    Open questions at the time
    • Structural basis of arginine methylation reading versus acetyl-lysine reading not resolved at atomic level
    • Breadth of methylarginine substrates recognized by BRD9 unknown
  13. 2025 High

    Showing that BRD9 recruits BRD2/BRD4 to chromatin and prevents R-loop accumulation at transcription-replication conflict sites established a genome stability function beyond homologous recombination.

    Evidence Co-IP, ChIP-seq, and DRIP-seq in leukemia cells showed BRD9 depletion reduces BRD2/BRD4 occupancy at R-loop-prone sites, causing R-loop accumulation and DNA damage

    PMID:40613709

    Open questions at the time
    • Whether R-loop resolution requires ncBAF ATPase activity or only BRD9-BET recruitment
    • No reconstituted system demonstrating BRD9-dependent R-loop prevention
  14. 2026 High

    Identifying lactylated H3K18 (H3K18la) as a physiologically relevant mark read by BRD9's bromodomain with transient affinity expanded the epigenetic reader code to include metabolic signaling through lactate-driven histone modification.

    Evidence NMR structural analysis showed H3K18la binds the conserved acetyl-lysine pocket with lower affinity than H3K18ac; multi-omics in hepatocellular carcinoma confirmed dynamic ncBAF recruitment to lactylation-marked enhancers

    PMID:41792243

    Open questions at the time
    • Whether transient H3K18la reading confers distinct transcriptional kinetics compared to stable H3K18ac reading
    • In vivo validation of lactylation-dependent BRD9 recruitment in non-cancer contexts

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of how BRD9's bromodomain discriminates among acetylated, methylated, and lactylated marks, and how the DUF3512 domain scaffolds the ncBAF complex, remain unresolved at atomic resolution.
  • No full-length BRD9 structure or cryo-EM structure of BRD9 within ncBAF
  • Mechanism by which BRD9 limits CTCF occupancy not biochemically reconstituted
  • Whether BRD9's non-histone reader functions operate within or outside the ncBAF complex context

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 7 GO:0140110 transcription regulator activity 5 GO:0098772 molecular function regulator activity 3
Localization
GO:0005634 nucleus 6 GO:0005694 chromosome 6
Pathway
R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 5 R-HSA-4839726 Chromatin organization 5 R-HSA-168256 Immune System 4 R-HSA-73894 DNA Repair 2
Partners
BRD4CTCFFOXP1GLTSCR1PPARARAD54RELASMARCA4
Complex memberships
ncBAF (GBAF) SWI/SNF complex

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 BRD9 is a bromodomain-containing subunit of the SWI/SNF chromatin remodeling complex BAF, and its bromodomain can be targeted by VHL-based PROTAC degraders (VZ185) that redirect E3 ubiquitin ligase activity to selectively degrade BRD9 within cells. PROTAC degrader design, ternary complex formation thermodynamics, cellular ubiquitination assays, kinetic profiling Journal of medicinal chemistry High 30540463
2017 BRD9 bromodomain can be targeted by cereblon E3 ubiquitin ligase-recruiting heterobifunctional degraders (dBRD9), achieving 10- to 100-fold enhanced potency over parental BRD9 bromodomain ligands in AML models. Heterobifunctional PROTAC design, cellular degradation assays, MS proteomics Angewandte Chemie (International ed. in English) High 28418626
2015 BRD9 contains a bromodomain that functions as an acetyl-lysine reader; I-BRD9 is a selective inhibitor (>700-fold selectivity over BET family, >200-fold over BRD7) identified by structure-based design that displaces BRD9 from chromatin and regulates oncology and immune response gene networks. Structure-based drug design, selectivity profiling across bromodomain panel, cellular chromatin displacement assays, gene expression profiling in Kasumi-1 cells Journal of medicinal chemistry High 25856009
2018 BRD9 defines a non-canonical BAF complex (GBAF) in mouse embryonic stem cells together with GLTSCR1 or GLTSCR1L, which is distinct from the canonical esBAF complex; GBAF co-localizes with regulators of naive pluripotency and BRD9 interacts with BRD4 in a bromodomain-dependent fashion to recruit GBAF to chromatin. Co-immunoprecipitation, ChIP-seq, genome-wide localization, inhibitor treatments, pluripotency functional assays Nature communications High 30510198
2019 BRD9 defines a SWI/SNF sub-complex lacking SMARCB1; SMARCB1 loss causes increased BRD9 incorporation into SWI/SNF; while BRD9's bromodomain is dispensable, its DUF3512 domain is essential for SWI/SNF complex integrity in the absence of SMARCB1, creating a specific vulnerability in SMARCB1-mutant rhabdoid tumors. Genome-wide CRISPR-Cas9 screen, domain deletion/mutation analysis, ChIP-seq, co-immunoprecipitation Nature communications High 31015438
2016 BRD9, as a subunit of the SWI-SNF chromatin remodeling complex, is required in AML cells to sustain MYC transcription; a bromodomain-swap resistance allele of BRD9 retains SWI/SNF functionality despite altered bromodomain pocket, establishing on-target BRD9 bromodomain engagement as the antiproliferative mechanism. Bromodomain-swap genetic engineering (allelic replacement), small-molecule inhibitor series, antiproliferative assays, MYC transcription measurement Nature chemical biology High 27376689
2020 Following DNA damage, the BRD9 bromodomain binds acetylated K515 on RAD54 and facilitates RAD54's interaction with RAD51, which is essential for homologous recombination (HR)-mediated DNA double-strand break repair. Co-immunoprecipitation, pulldown assays, HR reporter assays, BRD9 inhibitor (I-BRD9) treatment, RAD54 acetylation mapping Nature communications High 32457312
2020 BRD9 interacts with androgen receptor (AR) and CTCF, and the GBAF (ncBAF) complex exhibits overlapping genome localization with BET proteins to coordinate SWI/SNF-BET cooperation in AR-dependent gene expression in prostate cancer. Co-immunoprecipitation, ChIP-seq, BRD9 inhibitor/degrader treatment, xenograft tumor growth assays Cancer research High 33355184
2022 BRD9, as a subunit of the ncBAF complex, regulates interferon-stimulated genes (ISGs) in macrophages; BRD9 and BRD4 are cobound at ISG promoters and co-recruited upon endotoxin stimulation along with STAT1, STAT2, and IRF9 (ISGF3 complex); BRD9 inhibition or degradation reduces STAT1/STAT2/IRF9 binding at these loci. ChIP-seq, BRD9 inhibitor (BRD9i) and degrader (dBRD9) treatment, gene expression analysis, transcription factor binding assays Proceedings of the National Academy of Sciences of the United States of America High 34983841
2021 BRD9 colocalizes with GR at a subset of genomic binding sites in macrophages; depletion of BRD9 enhances GR occupancy at inflammatory-related genes, thereby potentiating GR-induced transcriptional repression, identifying BRD9 as a genomic antagonist of GR. ChIP-seq, BRD9 inhibition, degradation, and genetic deletion in macrophages, GR occupancy analysis, inflammatory gene expression profiling Proceedings of the National Academy of Sciences of the United States of America High 34446564
2015 Binding of a 9H-purine scaffold ligand to the BRD9 bromodomain causes an unprecedented rearrangement of residues forming the acetyllysine recognition site (induced-fit pocket), and displaces BRD9 from chromatin without affecting BRD4/histone complexes. Crystal structure determination, bioluminescence proximity assay, structure-based iterative design Journal of medicinal chemistry High 25703523
2019 BRD9 binds enhancer regions in a cell-type-specific manner in AML cells and sustains a STAT5 signaling pathway by regulating SOCS3 expression levels, which is required for leukemia cell survival. ChIP-seq, siRNA knockdown, gene expression profiling, apoptosis assays in AML cells and primary blasts Cell death & disease Medium 31000698
2021 In clear cell RCC, SOX17 recruits BRD9 to de novo super enhancers associated with oncogenic genes (CCND1, VEGFR2, CDC20, SRC, MAPK6); BRD9 mRNA is stabilized via FTO-mediated m6A demethylation in HIF2α-low ccRCC. CRISPR-Cas9 knockout screen in vivo, RNA-seq, ChIP-seq, m6A analysis Science translational medicine Medium 34586831
2023 BRD9 forms a complex with SMAD2/3, BRD4, β-CATENIN, and P300 to regulate TGF-β/Nodal/Activin and Wnt signaling pathways by controlling H3K27ac deposition on pluripotency and differentiation genes in human ESCs. Co-immunoprecipitation, ChIP-seq, H3K27ac profiling, BRD9 depletion/inhibition, rescue experiments with pathway ligands Nucleic acids research Medium 37870468
2023 BRD9 inhibition disrupts enhancer-promoter looping and transcription of stemness genes in pancreatic cancer stem-like cells, and mechanistically cooperates with TGF-β/Activin-SMAD2/3 signaling to orchestrate CSC stemness. Small molecule epigenetic screen, genetic ablation, 3D chromatin looping analysis, patient-derived xenografts Gastroenterology Medium 37739089
2019 CCAR2 acetylation by sulforaphane creates a binding site recognized by BRD9 (and BET family members); BRD9 acts as an acetyl reader of acetylated CCAR2, revealed by protein domain arrays and pull-down assays, contributing to a BET/BRD9 acetyl switch governing Wnt coactivator functions. Protein domain arrays, pull-down assays, Co-IP, BRD9 inhibitor treatment (JQ1/sulforaphane combination), colorectal cancer model Cancer research Medium 30643017
2023 BRD9 interacts with transcription factor FOXP1, activating Stat1 transcription and IFN-β signaling, thereby suppressing osteoclastogenesis through a negative feedback mechanism on RANKL-induced osteoclast differentiation. Co-immunoprecipitation, ChIP assays, myeloid-specific Brd9 conditional knockout mouse model, osteoclast differentiation assays Nature communications High 36918560
2023 BRD9 loss in hematopoietic stem cells enhances chromatin accessibility and significantly colocalizes with CTCF; BRD9 loss augments CTCF chromatin recruitment, leading to altered chromatin state and expression of myeloid-related genes within intact topologically associating domains. ChIP-seq, ATAC-seq, RNA-seq, Hi-C, conditional Brd9 knockout mouse model Nature communications High 38102116
2022 BRD9 inhibition downregulates fibroblast-related genes and decreases chromatin accessibility at somatic enhancers during human cell reprogramming; BRD9 maintains expression of transcriptional regulators MN1 and ZBTB38 that impede reprogramming, acting as a barrier to pluripotency. Genetic and chemical inhibition of BRD9, ATAC-seq, gene expression profiling, reprogramming efficiency assays Stem cell reports Medium 36332631
2025 BRD9 plays a pivotal role in recruiting BRD2 and BRD4 to chromatin through direct interactions, preventing R-loop formation during transcription; BRD9 depletion reduces BRD2/BRD4 occupancy at R-loop-prone sites, promoting R-loop accumulation, transcription-replication conflict, and DNA damage in leukemia cells. Co-immunoprecipitation, ChIP-seq, R-loop detection (DRIP-seq), PROTAC-based BRD9 degradation, proliferation and differentiation assays Nucleic acids research High 40613709
2025 BRD9 functions as a reader of methylated arginine-391 (R391) of AKT1 through an aromatic cage in its bromodomain, unexpectedly extending its reader function beyond acetyl-lysine; BRD9 and AKT co-regulate transcription through EZH2-mediated H3K27 methylation. Biochemical binding assays, bromodomain mutational analysis, RNA-seq, in vivo tumor growth assays, synergy assays with EZH2 inhibitors Science advances High 40279411
2025 BRD9 binds to HIV-1 LTR promoter and competes with HIV-1 Tat protein for binding to the HIV-1 genome, functioning as an HIV-1 latency regulator; BRD9 inhibition synergizes with BRD4 inhibition in inducing HIV-1 production. CUT&RUN DNA sequencing, transcriptomics, BRD9 inhibition/knockdown/degradation in T cell lines and primary CD4+ T cells, competition binding assays Proceedings of the National Academy of Sciences of the United States of America Medium 40402245
2022 Ultra-rare truncating loss-of-function variants in BRD9 impair IFN-stimulated gene expression and antiviral activity, establishing BRD9 as functionally required for full type I interferon signaling; full-length BRD9 but not truncated forms restore IFN-dependent antiviral response. BRD9 knockout and reconstitution model, functional IFN-stimulated gene expression assays, viral replication assays Scientific reports Medium 36100643
2022 BRD9 epigenetically coordinates H3K27ac modifications on promoter regions of glycolysis genes ENO2 and ALDOC, inducing enhanced glycolysis activity in colon adenocarcinoma cells. ChIP assay for H3K27ac at ENO2/ALDOC promoters, Seahorse metabolic flux analysis, BRD9 knockdown/overexpression, in vivo xenograft model Cancer medicine Medium 35778964
2025 BRD9 inhibits p53 nuclear translocation via direct binding, subsequently activating E2F transcription factors; E2F1 directly binds and transactivates the BRD9 promoter, establishing a positive BRD9-p53-E2F1 feedback loop in gastric cancer. Co-immunoprecipitation, subcellular fractionation, luciferase reporter assays, RNA sequencing Molecular cancer Medium 41039535
2024 BRD9 ncBAF complex regulates AML transcription through H3K27ac sensing by BRD9 bromodomain; BRD9 bromodomain activity maintains chromatin accessibility at gene promoters and distal enhancers at GATA, ETS, and AP-1 motifs, repressing myeloid maturation factors and tumor suppressor genes. BRD9 bromodomain inhibition, nascent transcription assays (TT-seq), ATAC-seq, CUT&RUN, in five AML cell lines Cancer research communications Medium 38126767
2025 BRD9 selectively recruits DCAF16 E3 ligase via a reversible covalent interaction at DCAF16 Cys58, facilitated by ternary complex formation with BRD9, enabling targeted protein degradation (molecular glue mechanism); BRD9 degradation is achieved in vivo after oral dosing. Co-immunoprecipitation-mass spectrometry, mutagenesis of DCAF16 Cys58, ternary complex analysis, in vivo xenograft mouse model with oral dosing Nature communications High 41145412
2025 BRD9 loss in SF3B1-mutant hematopoiesis enhances CTCF occupancy at the ALOX5 locus boundary via aberrant chromatin loop formation (revealed by Hi-C), driving transcriptional activation of ALOX5 and increased lipid peroxidation/ferroptosis susceptibility. RNA-seq, ChIP-seq, Hi-C, BODIPY-C11 lipid peroxidation assay, BRD9 depletion mouse models International journal of hematology Medium 41219678
2026 BRD9's bromodomain reads lactate-induced H3K18 lactylation (H3K18la) with transient affinity through its conserved acetyl-lysine pocket (distinct from stable H3K18ac binding), dynamically recruiting ncBAF to active enhancers/promoters to drive oncogenic transcription in hepatocellular carcinoma. NMR structural analysis, biophysical binding assays, multi-omics (ATAC-seq, ChIP-seq, RNA-seq), BRD9 targeting experiments in HCC Cell death and differentiation High 41792243
2025 PPARα interacts with ncBAF via BRD9; BRD9 negatively regulates PPARα-mediated transactivation of fatty acid oxidation genes (including CPT1A) by restricting chromatin accessibility at PPRE elements; BRD9 inhibition enhances PPARα binding to CPT1A PPRE. Glycerol sedimentation assay, co-immunoprecipitation, pull-down assays, ChIP-qPCR, FAIRE-qPCR, BRD9 inhibitor (BI-9564) treatment in HepG2 and primary hepatocytes, in vivo mouse model Journal of lipid research High 40780491
2025 BRD9 binds RELA and potentiates expression of downstream antiviral genes in glioblastoma, creating resistance to oncolytic herpes simplex virus; BRD9 knockout or inhibition suppresses antiviral gene expression and enhances oncolytic virus efficacy. CRISPR screening, co-immunoprecipitation (BRD9-RELA), transcriptomic analysis, in vitro and in vivo GBM models Cell reports. Medicine Medium 40744020
2024 BRD9 interacts with FOXP1 to regulate CST1 expression and downstream PI3K/AKT signaling in gallbladder cancer, as demonstrated by ChIP-qPCR showing BRD9 occupancy at CST1 promoter and co-interaction with FOXP1. siRNA knockdown, ChIP-qPCR, RNA sequencing, in vivo xenograft model, FOXP1-BRD9 interaction assay Gene therapy Medium 39306629
2019 BRD9 is found in the SWI/SNF complex bound to the MYC super-enhancer locus in PIK3CA/KRAS double-mutant breast epithelial cells; small molecule inhibition of BRD9 reduces MYC transcript levels and anchorage-independent growth dependent on BRD9 expression. ChIP at MYC super-enhancer, CRISPR-Cas9 BRD9 manipulation, BRD9 inhibitor treatment, anchorage-independent growth assays Cancers Medium 31652979
2024 BRD9 promotes MYC target gene expression in multiple myeloma by predominantly occupying promoter regions of ribosome biogenesis genes and cooperating with BRD4 to enhance MYC transcriptional function. shRNA knockdown, PROTAC degrader (dBRD9-A), ChIP-seq at ribosome biogenesis gene promoters, RNA-seq, in vivo xenograft Clinical cancer research Medium 36780189
2022 Pharmacological BRD9 inhibition in macrophages disrupts BRD9 and SMARCA4 occupancy at melanocyte-specific chromatin loci, repressing pigmentation-specific gene expression and melanin synthesis. ChIP assays for BRD9 and SMARCA4, iBRD9 treatment, BRD9 depletion, gene expression profiling in melanoblasts and melanocytes Pigment cell & melanoma research Medium 36112085

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Iterative Design and Optimization of Initially Inactive Proteolysis Targeting Chimeras (PROTACs) Identify VZ185 as a Potent, Fast, and Selective von Hippel-Lindau (VHL) Based Dual Degrader Probe of BRD9 and BRD7. Journal of medicinal chemistry 250 30540463
2017 Degradation of the BAF Complex Factor BRD9 by Heterobifunctional Ligands. Angewandte Chemie (International ed. in English) 220 28418626
2015 Discovery of I-BRD9, a Selective Cell Active Chemical Probe for Bromodomain Containing Protein 9 Inhibition. Journal of medicinal chemistry 186 25856009
2018 A non-canonical BRD9-containing BAF chromatin remodeling complex regulates naive pluripotency in mouse embryonic stem cells. Nature communications 174 30510198
2019 BRD9 defines a SWI/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors. Nature communications 167 31015438
2016 Sensitivity and engineered resistance of myeloid leukemia cells to BRD9 inhibition. Nature chemical biology 156 27376689
2019 miR-140-3p functions as a tumor suppressor in squamous cell lung cancer by regulating BRD9. Cancer letters 73 30660651
2020 BRD9 Is a Critical Regulator of Androgen Receptor Signaling and Prostate Cancer Progression. Cancer research 63 33355184
2020 The bromodomain containing protein BRD-9 orchestrates RAD51-RAD54 complex formation and regulates homologous recombination-mediated repair. Nature communications 61 32457312
2021 Aberrant activation of m6A demethylase FTO renders HIF2αlow/- clear cell renal cell carcinoma sensitive to BRD9 inhibitors. Science translational medicine 57 34586831
2019 BRD9 binds cell type-specific chromatin regions regulating leukemic cell survival via STAT5 inhibition. Cell death & disease 53 31000698
2015 9H-purine scaffold reveals induced-fit pocket plasticity of the BRD9 bromodomain. Journal of medicinal chemistry 51 25703523
2019 GSK2801, a BAZ2/BRD9 Bromodomain Inhibitor, Synergizes with BET Inhibitors to Induce Apoptosis in Triple-Negative Breast Cancer. Molecular cancer research : MCR 49 31000582
2017 BRD9 Inhibition, Alone or in Combination with Cytostatic Compounds as a Therapeutic Approach in Rhabdoid Tumors. International journal of molecular sciences 48 28714904
2022 BRD9 degraders as chemosensitizers in acute leukemia and multiple myeloma. Blood cancer journal 42 35853853
2023 BRD9-mediated chromatin remodeling suppresses osteoclastogenesis through negative feedback mechanism. Nature communications 40 36918560
2022 BRD9 regulates interferon-stimulated genes during macrophage activation via cooperation with BET protein BRD4. Proceedings of the National Academy of Sciences of the United States of America 39 34983841
2020 Targeting BRD9 for Cancer Treatment: A New Strategy. OncoTargets and therapy 35 33380808
2021 Insights into the Ligand Binding to Bromodomain-Containing Protein 9 (BRD9): A Guide to the Selection of Potential Binders by Computational Methods. Molecules (Basel, Switzerland) 34 34885774
2021 Bromodomain containing 9 (BRD9) regulates macrophage inflammatory responses by potentiating glucocorticoid receptor activity. Proceedings of the National Academy of Sciences of the United States of America 33 34446564
2023 BRD9 determines the cell fate of hematopoietic stem cells by regulating chromatin state. Nature communications 32 38102116
2020 Application of Atypical Acetyl-lysine Methyl Mimetics in the Development of Selective Inhibitors of the Bromodomain-Containing Protein 7 (BRD7)/Bromodomain-Containing Protein 9 (BRD9) Bromodomains. Journal of medicinal chemistry 32 32410449
2019 Acetylation of CCAR2 Establishes a BET/BRD9 Acetyl Switch in Response to Combined Deacetylase and Bromodomain Inhibition. Cancer research 31 30643017
2023 BRD9 Degradation Disrupts Ribosome Biogenesis in Multiple Myeloma. Clinical cancer research : an official journal of the American Association for Cancer Research 28 36780189
2018 Insight into selective mechanism of class of I-BRD9 inhibitors toward BRD9 based on molecular dynamics simulations. Chemical biology & drug design 27 30225973
2021 The BRD9/7 Inhibitor TP-472 Blocks Melanoma Tumor Growth by Suppressing ECM-Mediated Oncogenic Signaling and Inducing Apoptosis. Cancers 26 34771678
2019 PIK3CA Cooperates with KRAS to Promote MYC Activity and Tumorigenesis via the Bromodomain Protein BRD9. Cancers 26 31652979
2023 BRD9 Inhibition Attenuates Matrix Degradation and Pyroptosis in Nucleus Pulposus by Modulating the NOX1/ROS/NF-κB axis. Inflammation 23 36801999
2023 BRD9-SMAD2/3 Orchestrates Stemness and Tumorigenesis in Pancreatic Ductal Adenocarcinoma. Gastroenterology 23 37739089
2023 BRD9-mediated control of the TGF-β/Activin/Nodal pathway regulates self-renewal and differentiation of human embryonic stem cells and progression of cancer cells. Nucleic acids research 22 37870468
2022 BRD9 is an essential regulator of glycolysis that creates an epigenetic vulnerability in colon adenocarcinoma. Cancer medicine 19 35778964
2021 Targeting BRD9 by I-BRD9 efficiently inhibits growth of acute myeloid leukemia cells. Translational cancer research 19 35116642
2023 Epigenetic modulation by targeting bromodomain containing protein 9 (BRD9): Its therapeutic potential and selective inhibition. International journal of biological macromolecules 17 36709803
2024 Discovery of CW-3308 as a Potent, Selective, and Orally Efficacious PROTAC Degrader of BRD9. Journal of medicinal chemistry 16 39132814
2021 BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors. Cell death & disease 16 34667163
2024 Discovery of a Highly Potent and Selective BRD9 PROTAC Degrader Based on E3 Binder Investigation for the Treatment of Hematological Tumors. Journal of medicinal chemistry 15 38913763
2024 Programmed BRD9 Degradation and Hedgehog Signaling Activation via Silk-Based Core-Shell Microneedles Promote Diabetic Wound Healing. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 15 39413023
2022 BRD9-containing non-canonical BAF complex maintains somatic cell transcriptome and acts as a barrier to human reprogramming. Stem cell reports 14 36332631
2022 Identification of 2,4,5-trisubstituted-2,4-dihydro-3H-1,2,4-triazol-3-one-based small molecules as selective BRD9 binders. European journal of medicinal chemistry 14 36577218
2024 The ncBAF Complex Regulates Transcription in AML Through H3K27ac Sensing by BRD9. Cancer research communications 13 38126767
2023 Exploring the chemical space of functionalized [1,2,4]triazolo[4,3-a]quinoxaline-based compounds targeting the bromodomain of BRD9. Bioorganic chemistry 13 37352721
2023 Structure-based identification of new orally bioavailable BRD9-PROTACs for treating acute myelocytic leukemia. European journal of medicinal chemistry 13 39491427
2021 Introducing structure-based three-dimensional pharmacophore models for accelerating the discovery of selective BRD9 binders. Bioorganic chemistry 13 34823196
2016 Development of chemical probes for the bromodomains of BRD7 and BRD9. Drug discovery today. Technologies 12 27769361
2022 BRD9 Inhibition by Natural Polyphenols Targets DNA Damage/Repair and Apoptosis in Human Colon Cancer Cells. Nutrients 11 36297001
2016 An Advanced Tool To Interrogate BRD9. Journal of medicinal chemistry 11 27120693
2022 Circ_CSPP1 Regulates the Development of Non-small Cell Lung Cancer via the miR-486-3p/BRD9 Axis. Biochemical genetics 10 35678942
2024 Identification and Development of BRD9 Chemical Probes. Pharmaceuticals (Basel, Switzerland) 9 38543178
2024 BRD9 promotes the progression of gallbladder cancer via CST1 upregulation and interaction with FOXP1 through the PI3K/AKT pathway and represents a therapeutic target. Gene therapy 9 39306629
2022 Identification of Selective BRD9 Inhibitor via Integrated Computational Approach. International journal of molecular sciences 9 36362300
2018 Molecular mechanism study of several inhibitors binding to BRD9 bromodomain based on molecular simulations. Journal of biomolecular structure & dynamics 9 30058436
2024 Synergy between BRD9- and IKZF3-Targeting as a Therapeutic Strategy for Multiple Myeloma. Cancers 8 38610997
2021 Exploring the Value of BRD9 as a Biomarker, Therapeutic Target and Co-Target in Prostate Cancer. Biomolecules 8 34944438
2025 Discovery of BRD9 Molecular Glue Degraders That Spare Cardiomyocytes. Journal of the American Chemical Society 7 40960846
2020 BRD9 controls the oxytocin signaling pathway in gastric cancer via CANA2D4, CALML6, GNAO1, and KCNJ5. Translational cancer research 7 35117701
2022 Epigenetic and pharmacological control of pigmentation via Bromodomain Protein 9 (BRD9). Pigment cell & melanoma research 6 36112085
2019 Design, synthesis and biological evaluation of imidazo[1,5-a]pyrazin-8(7H)-one derivatives as BRD9 inhibitors. Bioorganic & medicinal chemistry 6 30824168
2025 In-depth functional analysis of BRD9 in fetal hematopoiesis reveals context-dependent roles. iScience 5 40109374
2025 Mode of action of a DCAF16-recruiting targeted glue that can selectively degrade BRD9. Nature communications 5 41145412
2024 BI-7273, a BRD9 inhibitor, reduces lipid accumulation by downregulating the AKT/mTOR/SREBP1 signaling pathway. Biochemical pharmacology 5 38971334
2025 Prostate cancer exploits BRD9-driven metabolic reprogramming to shape the aggressive phenotype. Cell death & disease 4 40263302
2023 BRD9 status is a major contributor for cysteine metabolic remodeling through MST and EAAT3 modulation in malignant melanoma. Biochimica et biophysica acta. Molecular basis of disease 4 38070581
2022 Ultra-Rare BRD9 Loss-of-Function Variants Limit the Antiviral Action of Interferon. Scientific reports 4 36100643
2025 BRD9 inhibition as potential treatment option for testicular germ cell tumors. Andrology 3 40167526
2025 Discovery of CFT8634, a Potent, Selective, and Orally Bioavailable Heterobifunctional Degrader of BRD9. Journal of medicinal chemistry 3 41285423
2024 BRD9 regulates normal human hematopoietic stem cell function and lineage differentiation. Cell death and differentiation 3 38816579
2024 Unveiling Allosteric Regulation and Binding Mechanism of BRD9 through Molecular Dynamics Simulations and Markov Modeling. Molecules (Basel, Switzerland) 3 39124901
2025 BRD9 promotes the malignant phenotype of thyroid cancer by activating the MAPK/ERK pathway. Anti-cancer drugs 2 39903580
2025 Unveiling New Triazoloquinoxaline-Based PROTACs Designed for the Selective Degradation of the ncBAF Chromatin Remodeling Subunit BRD9. Chemistry (Weinheim an der Bergstrasse, Germany) 2 40343767
2025 BRD9 functions as an HIV-1 latency regulatory factor. Proceedings of the National Academy of Sciences of the United States of America 2 40402245
2025 BRD9 inhibition overcomes oncolytic virus therapy resistance in glioblastoma. Cell reports. Medicine 2 40744020
2025 STAT3 induced BRD9 activation promotes intrahepatic cholangiocarcinoma progression by enhancing CD36 controlled fatty acid metabolism. Cancer letters 2 41033607
2024 In Silico Design, Chemical Synthesis, Biophysical and in Vitro Evaluation for the Identification of 1-Ethyl-1H-Pyrazolo[3,4-b]Pyridine-Based BRD9 Binders. ChemPlusChem 2 39119716
2025 Brd9 antagonism induces beige adipocytes in white adipose tissues and protects against diet-induced obesity. Obesity (Silver Spring, Md.) 1 40176372
2025 BRD9 functions as a methylarginine reader to regulate AKT-EZH2 signaling. Science advances 1 40279411
2025 Depletion of BRD9-mediated R-loop accumulation inhibits leukemia cell growth via transcription-replication conflict. Nucleic acids research 1 40613709
2025 BRD9-p53-E2F1 circuit orchestrates cell growth and DNA damage repair in gastric cancer. Molecular cancer 1 41039535
2025 BRD9 depletion-mediated ALOX5 upregulation via chromatin dysregulation induces ferroptosis in SF3B1-mutant hematopoiesis. International journal of hematology 1 41219678
2025 Key imidazolyl groups that induce phenylalanine flipping enhance the efficacy of oral BRD9 inhibitors for AML treatment. Acta pharmaceutica Sinica. B 1 41477332
2024 TPPP-BRD9 fusion-related gallbladder carcinomas are frequently associated with intracholecystic neoplasia, neuroendocrine carcinoma, and a distinctive small tubular-type adenocarcinoma commonly accompanied with a syringomatous pattern. Human pathology 1 38972607
2026 BRD9 at the crossroads of splicing, chromatin remodeling, and hematopoiesis. Proceedings of the Japan Academy. Series B, Physical and biological sciences 0 41672512
2026 A 5-Br-1-Propylisatin Derivative as a Promising BRD9 Ligand: Insights from Computational and STD NMR Investigation. Molecules (Basel, Switzerland) 0 41752361
2026 BRD9 recognizes lactate-induced H3K18 lactylation to drive oncogenic chromatin remodeling in hepatocellular carcinoma. Cell death and differentiation 0 41792243
2026 The dual role of BRD9 in cancer: Mechanistic insights and therapeutic prospects. iScience 0 41797932
2026 Virtual screening and cellular validation of dolutegravir as a BRD9 inhibitor for attenuating pyroptosis in peritoneal mesothelial cells. Renal failure 0 41943612
2026 Aberrant activation of epigenetic BRD9-DGAT1 axis promotes lipid droplets deposition and ferroptosis resistance in YAP-high prostate cancer. Cell death & disease 0 41980921
2025 Chromatin remodeler BRD9 represses transcription of PPARα target genes, including CPT1A to suppress lipid metabolism. Journal of lipid research 0 40780491
2025 Integrative analysis reveals synergistic regulation of Sp7 by BRD9 and Wnt/β-catenin signaling during osteogenic differentiation. Communications biology 0 41326797
2025 The future of BRD9 inhibitors: a patent perspective (2019-present). Expert opinion on therapeutic patents 0 41409030
2025 SS18::SSX and BRD9 Modulate Synovial Sarcoma Differentiation. Cells 0 41440042
2023 BRD9-SMAD2/3 orchestrates stemness and tumorigenesis in pancreatic ductal adenocarcinoma. bioRxiv : the preprint server for biology 0 36909530