2022年8月1日 · GNE-987 inhibited AML cell proliferation by inhibiting the cell cycle and inducing apoptosis. BRD2, BRD3, and BRD4 were consistent with decreased VHL (Von Hippel Lindau) expression in AML cells. In an AML xenograft model, GNE-987 significantly reduced the hepatosplenic infiltration of leukemia cells and increased the mouse survival time.

GNE-987 is a PROTAC connected by ligands for von Hippel-Lindau and BRD4. GNE-987 exhibits picomolar cell BRD4 degradation activity (DC50 =0.03 nM for EOL-1 AML cell line). GNE-987 binds equipotently to the BD1 and BD2 bromodomains of BRD4 with low nanomolar affinities (IC50 =4.7 and 4.4 nM, respectively).

2022年7月16日 · Using the BRD4 inhibitor GNE-987, we assessed the dependence of AML cells on transcriptional activation for growth and found GNE-987 treatment predominantly inhibits cell growth in AML cells.

In an AML xenograft model, GNE-987 significantly reduced the hepatosplenic infiltration of leukemia cells and increased the mouse survival time. Based on analysis of RNA-seq and ChIP-seq analyses, GNE-987 could target multiple SE- (super-enhancer-) related genes, including LYL1 (lymphoblastic leukemia 1), to inhibit AML.

In the AML xenograft model, GNE-987 significantly reduced the liver and spleen infiltration of leukemia cells, increased the survival time of mice, and caused BRD4, Ki67 dysregulation and caspase3 activation. According to the analysis of RNA-seq and ChIP-seq, GNE-987 can inhibit AML by targeting numerous super-enhancers.

GNE-987 inhibited AML cell proliferation by inhibiting the cell cycle and inducing apoptosis. BRD2, BRD3, and BRD4 were consistent with decreased VHL (Von Hippel Lindau) expression in AML cells. In an AML xenograft model, GNE-987 significantly reduced the hepatosplenic infiltration of leukemia cells and increased the mouse survival time.

2022年8月1日 · GNE-987 inhibited AML cell proliferation by inhibiting the cell cycle and inducing apoptosis. BRD2, BRD3, and BRD4 were consistent with decreased VHL (Von Hippel Lindau) expression in AML cells. In an AML xenograft model, GNE-987 significantly reduced the hepatosplenic infiltration of leukemia cells and increased the mouse survival time.

GNE-987 是一种 BRD4 降解 PROTAC，由 BRD4B1 和 BRD4B2（BRD4 溴结构域 1 和 2）以及 VHL E3-泛素连接酶组成。 它对 EOL-1 AML 细胞系表现出 BRD4 降解活性，DC50 为 0.03 nM。 GNE-987 通过促进 BRD4 的快速和持续降解并抑制其下游靶标来抑制细胞增殖并诱导细胞凋亡。

GNE-987 is a PROTAC connected by ligands for von Hippel-Lindau and BRD4. GNE-987 exhibits picomolar cell BRD4 degradation activity (DC50=0.03 nM for EOL-1 AML cell line). GNE-987 binds equipotently to the BD1 and BD2 bromodomains of BRD4 with low nanomolar affinities (IC50=4.7 and 4.4 nM, respectively).

2022年8月1日 · In an AML xenograft model, GNE-987 significantly reduced the hepatosplenic infiltration of leukemia cells and increased the mouse survival time. Based on analysis of RNA-seq and ChIP-seq...