brd9 protein degradation compounds  (C4 Therapeutics)

Journal: Biochemistry

Article Title: Molecular Glues: The Adhesive Connecting Targeted Protein Degradation to the Clinic

doi: 10.1021/acs.biochem.2c00245

Figure Lengend Snippet: Notable Molecular Glue-Related Patents

Article Snippet: WO 2021/178920 , compounds for targeted degradation of BRD9 , C4 Therapeutics , BRD9 protein degradation compounds provided for treatment of disorders mediated by BRD9, including abnormal cellular proliferation.

Techniques: Binding Assay, Ubiquitin Proteomics, Synthesized, Modification, Protein Binding, Activity Assay

Journal: Nature Communications

Article Title: Genomic characterization of genes encoding histone acetylation modulator proteins identifies therapeutic targets for cancer treatment

doi: 10.1038/s41467-019-08554-x

Figure Lengend Snippet: Identification of BRD9 as a potential therapeutic target for cancer treatment. a Expression levels of BRD9 mRNA in nine cancer types in which BRD9 was focally amplified. Gray: normal controls; white: tumors without BRD9 amplification; red: tumors with BRD9 amplification. BRD9 copy number status in each tumor specimen was estimated by a GISTIC analysis. b Expression of BRD9 protein was retrieved from the Human Protein Atlas dataset. A typical immunohistochemical staining of each cancer type is presented. Scale bar indicates 100 μm. c The heatmap of the genes that were significantly, positively co-expressed with BRD9 in nine cancer types. Each tumor is represented in a column and each gene in a row. The RNA expression of BRD9 is presented as a bar graph under the heatmap. The genes were arranged from top to bottom in descending order of their correlation with BRD9 . d The pathways over-represented for BRD9 -associated genes at the pan-cancer and individual cancer levels, according to pre-ranked gene-set enrichment analysis. e The functional hubs of pathways associated with BRD9 expression as analyzed by pre-ranked gene set enrichment. f BRD9 was knocked down with two independent shRNAs in four different breast and ovarian cancer cell lines. Knockdown efficiency was confirmed by real-time RT-PCR. g Four-day growth curves of cancer cell lines transfected with control or BRD9 -specific shRNAs. h , i Soft agar assays of MDA-MB-231 ( h ) and OVCAR8 ( i ) cells expressing control and BRD9 -specific hairpins. Scale bar indicates 1 cm. Quantification of the number of colonies from the soft agar assays on MDA-MB-231 ( h ) and OVCAR8 ( i ) cells. j In vivo xenograft tumor growth curve of MDA-MB-231 (upper) and OVCAR8 (lower) cells expressing control and BRD9 -specific hairpins. k Representative pictures of tumors derived from control and BRD9 -specific hairpin-expressing cells. Scale bar indicates 1 cm. l In vivo tumor weight curves for MDA-MB-231 (upper) and OVCAR8 (lower) cells expressing control and BRD9 -specific hairpins. m Knockdown efficiency of xenograft tumors was confirmed by real-time RT-PCR. * t -test p -value < 0.05

Article Snippet: BRD9 copy number status in each tumor specimen was estimated by a GISTIC analysis. b Expression of BRD9 protein was retrieved from the Human Protein Atlas dataset.

Techniques: Expressing, Amplification, Immunohistochemical staining, Staining, RNA Expression, Functional Assay, Knockdown, Quantitative RT-PCR, Transfection, Control, In Vivo, Derivative Assay