Selective inhibitors of bromodomain-containing protein 9 (BRD9) may have therapeutic potential in the treatment of human malignancies and inflammatory diseases. A selective small molecule inhibitor that is well tolerated and has proper pharmacokinetic properties is required to explore the function of BRD9 in diseases. BI-9564 (2) is a cell permeable and noncytotoxic BRD9 inhibitor provided to the scientific community to explore BRD9 biology and determine its potential as a drug target.
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Identification of assembly mode of non-canonical BAF (ncBAF) chromatin remodeling complex core module.
Biochem Biophys Res Commun
January 2025
State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Science, and College of Life Sciences, Nankai University, 94 Weijin Road, Tianjin, 300071, China. Electronic address:
Mammalian SWI/SNF (mSWI/SNF) ATP-dependent chromatin remodeling complexes play critical roles in regulating gene expression and DNA accessibility, and more than 20 % of cancers have mutations in genes encoding chromatin remodeling complexes. The mSWI/SNF family comprises three distinct classes: canonical BAF (cBAF), PBAF, and non-canonical BAF (ncBAF). While the structures of cBAF and PBAF have been resolved by using cryo-electron microscopy (cryo-EM), the modular organization and assembly mechanism of ncBAF remain poorly understood.
View Article and Find Full Text PDFA Phase 1 Study of FHD-609, a Heterobifunctional Degrader of Bromodomain-Containing Protein 9, in Patients With Advanced Synovial Sarcoma or SMARCB1-Deficient Tumors.
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Dana-Farber Cancer Institute, Boston, United States.
Purpose: FHD-609, a potent, selective, heterobifunctional degrader of bromodomain-containing protein 9 (BRD9), was evaluated for treatment of patients with advanced synovial sarcoma (SS) or SMARCB1-deficient tumors.
Patients And Methods: In this multinational, open-label, phase 1 study (NCT04965753), patients received FHD609 intravenously at escalating doses either twice weekly (BIW) (5 to 80 mg; n=40) or once weekly (QW) (40 to 120 mg; n=15).
Results: Fifty-five patients received FHD-609 for a median of 43 days.
Scalp acupuncture alleviates remote hippocampal damage in MCAO rats by inhibiting neuroinflammation: A TMT-based proteomics analysis.
Neuroscience
December 2024
Department of Rehabilitation Medicine, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province, China. Electronic address:
While mounting evidence suggests that scalp acupuncture (SA) may be effective in alleviating neurological deficits in patients with acute ischemic stroke (IS), its effect on remote hippocampal damage in acute IS and the underlying mechanisms remain elusive. Thus, proteomics analysis was conducted to identify potential targets of SA therapy in acute IS. SA significantly reduced cerebral infarct volume and attenuated neuronal damage in the ischemic penumbra and hippocampus, as well as alleviated neurological deficits in rats with middle cerebral artery occlusion (MCAO).
View Article and Find Full Text PDFStructure-based identification of new orally bioavailable BRD9-PROTACs for treating acute myelocytic leukemia.
Eur J Med Chem
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Hangzhou Institute of Innovative Medicine, Institute of Drug Discovery and Design, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, PR China. Electronic address:
BRD9 is essential in regulating gene transcription and chromatin remodeling, and blocking BRD9 profoundly affects the survival of AML cells. However, the inhibitors of BRD9 suffer from various drawbacks, including poor phenotype and selectivity, and BRD9 PROTACs still face the challenge of druggability, which limits the development of blocking BRD9 in AML. This study described an oral activity BRD9 PROTAC C6 by recruiting the highly efficient E3 ligase.
View Article and Find Full Text PDFProgrammed BRD9 Degradation and Hedgehog Signaling Activation via Silk-Based Core-Shell Microneedles Promote Diabetic Wound Healing.
Adv Sci (Weinh)
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Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai Engineering Research Center of Advanced Dental Technology and Materials, Shanghai, 200125, China.
Wound healing impairment in diabetes mellitus is associated with an excessive inflammatory response and defective regeneration capability with suppressed Hedgehog (Hh) signaling. The bromodomain protein BRD9, a subunit of the non-canonical BAF chromatin-remodeling complex, is critical for macrophage inflammatory response. However, whether the epigenetic drug BRD9 degrader can attenuate the sustained inflammatory state of wounds in diabetes remains unclear.
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