An Advanced Tool To Interrogate BRD9

Karim, Rezaul M.; Schönbrunn, E.

doi:10.1021/acs.jmedchem.6b00550

Cited by 13 publications

(10 citation statements)

References 15 publications

(23 reference statements)

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“…For example, small-molecule inhibitors of the BRD9 bromodomain selectively suppress tumor cell proliferation and survival and induce apoptosis. 27,75,102,103 Indeed, scientists have researched and developed several effective BRD9 bromodomain inhibitors, such as BRD9 selective inhibitors (I-BRD9, 104 BI-7273, 105 and BI-9564 106 ) and BRD7/9 inhibitors. 107,108 LP99 is the first reported selective BRD7/9 inhibitor that effectively inhibits the binding of BRD7/9 to acetylated histones in vivo and in vitro; Moreover, LP99 inhibits the secretion of proinflammatory cytokine IL-6.…”

Section: Cancer Therapeutics For Targeting Brd9mentioning

confidence: 99%

“…BRD9 inhibitors, BI-7273 and BI-9564, used to investigate the biological functions of BRD9 in vivo and in vitro were proven to be non-toxic by fragment-based screening. 105,106 Based on the structural design, I-BRD9 has been identified as a selective cytochemical probe for BRD9. 113 In addition, I-BRD9 downregulates cancer and immunology-related genes, such as SAMSN1, 114 CLEC1, 115 FES, 116 and DUSP6.…”

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confidence: 99%

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Targeting BRD9 for Cancer Treatment: A New Strategy

Zhu¹,

Liao²,

Tang³

2020

OTT

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Bromodomain-containing protein 9 (BRD9) is a newly identified subunit of the non-canonical barrier-to-autointegration factor (ncBAF) complex and a member of the bromodomain family IV. Studies have confirmed that BRD9 plays an oncogenic role in multiple cancer types, by regulating tumor cell growth. The tumor biological functions of BRD9 are mainly due to epigenetic modification mediated by its bromodomain. The bromodomain recruits the ncBAF complex to the promoter to regulate gene transcription. This review summarizes the potential mechanisms of action of BRD9 in carcinogenesis and the emerging strategies for targeting BRD9 for cancer therapeutics. Although the therapeutic potential of BRD9 has been exploited to some extent, research on the detailed biological mechanisms of BRD9 is still in its infancy. Therefore, targeting BRD9 to study its biological roles will be an attractive tool for cancer diagnosis and treatment, but it remains a great challenge.

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Section: Cancer Therapeutics For Targeting Brd9mentioning

confidence: 99%

mentioning

confidence: 99%

Targeting BRD9 for Cancer Treatment: A New Strategy

Zhu¹,

Liao²,

Tang³

2020

OTT

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“…For instance, BRD9 has been identified as a subunit of the mammalian SWI/SNF chromatin remodelling complex [38] involved in organismal development, gene regulation, and cell lineage specification, which seems to be involved in tumour suppression [39]. BRD9 is found overexpressed in numerous cancers and this overexpression seems to be associated with susceptibility to lung cancer, synovial sarcoma, and breast cancer [40][41][42], indicating that BRD9 has a potential oncogenic effect.…”

Section: Discussionmentioning

confidence: 99%

High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma

Campos¹,

Fragoso²,

Luís³

et al. 2020

Genes

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Cutaneous melanoma is one of the most aggressive human cancers due to its high invasiveness. Germline mutations in high-risk melanoma susceptibility genes have been associated with development hereditary melanoma; however, most genetic culprits remain elusive. To unravel novel susceptibility genes for hereditary melanoma, we performed whole exome sequencing (WES) on eight patients with multiple primary melanomas, high number of nevi, and negative for high and intermediate-risk germline mutations. Thirteen new potentially pathogenic variants were identified after bioinformatics analysis and validation. CDH23, ARHGEF40, and BRD9 were identified as the most promising susceptibility genes in hereditary melanoma. In silico analysis of CDH23 and ARHGEF40 variants provided clues for altered protein structure and function associated with the identified mutations. Then, we also evaluated the clinical value of CDH23, ARHGEF40, and BRD9 expression in sporadic melanoma by using the TCGA dataset (n = 461). No differences were observed in BRD9 expression between melanoma and normal skin samples, nor with melanoma stage, whereas ARHGEF40 was found overexpressed, and CDH23 was downregulated and its loss was associated with worse survival. Altogether, these results reveal three novel genes with clinical relevance in hereditary and sporadic melanoma.

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“…A team from industry and academia has now designed an in vivo active inhibitor of the BET family member BRD9, a component of the SWI/SNF complex BI-9564 [ 25 ]. The selective small molecule inhibitor is well tolerated and has appropriate pharmacokinetic properties for it to be used to explore the function of BRD9 in disease models [ 26 ]. The SGC has now made this chemical probe freely available at http://www.thesgc.org/chemical-probes to the scientific community to explore BRD9 biology.…”

Section: High-quality Chemical Tools Helpmentioning

confidence: 99%

Establishing a reliable framework for harnessing the creative power of the scientific crowd

Carter

Donner²,

Lee

et al. 2017

PLoS Biol

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Discovering new medicines is difficult and increasingly expensive. The pharmaceutical industry has responded to this challenge by embracing open innovation to access external ideas. Historically, partnerships were usually bilateral, and the drug discovery process was shrouded in secrecy. This model is rapidly changing. With the advent of the Internet, drug discovery has become more decentralised, bottom-up, and scalable than ever before. The term open innovation is now accepted as just one of many terms that capture different but overlapping levels of openness in the drug discovery process. Many pharmaceutical companies recognise the advantages of revealing some proprietary information in the form of results, chemical tools, or unsolved problems in return for valuable insights and ideas. For example, such selective revealing can take the form of openly shared chemical tools to explore new biological mechanisms or by publicly admitting what is not known in the form of an open call. The essential ingredient for addressing these problems is access to the wider scientific crowd. The business of crowdsourcing, a form of outsourcing in which individuals or organisations solicit contributions from Internet users to obtain ideas or desired services, has grown significantly to fill this need and takes many forms today. Here, we posit that open-innovation approaches are more successful when they establish a reliable framework for converting creative ideas of the scientific crowd into practice with actionable plans.

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An Advanced Tool To Interrogate BRD9

Cited by 13 publications

References 15 publications

Targeting BRD9 for Cancer Treatment: A New Strategy

Targeting BRD9 for Cancer Treatment: A New Strategy

High-Throughput Sequencing Identifies 3 Novel Susceptibility Genes for Hereditary Melanoma

Establishing a reliable framework for harnessing the creative power of the scientific crowd

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