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Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [RNA-Seq]

ABSTRACT: Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [RNA-Seq]

PROVIDER: PRJNA977982 | ENA |

REPOSITORIES: ENA

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Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [ATAC-Seq]

Project description:KAT6A, and its paralog KAT6B, are histone lysine acetyltransferases (HAT) that acetylate histone H3K23 and regulate diverse biological processes including transcription, cell-cycle progression, and stem cell development. KAT6A exerts an oncogenic role in several tumor types including breast cancer where it is amplified in 10-15% of patients. However, pharmacologic targeting of KAT6A to achieve therapeutic benefit has been a challenge. Here we describe identification of a highly potent, selective and orally bioavailable KAT6A/KAT6B inhibitor CTx-648 (PF-9363), derived from a novel benzisoxazole series, which demonstrates anti-tumor activity in correlation with H3K23Ac inhibition in KAT6A over-expressing breast cancer. Transcriptional and epigenetic profiling studies show reduced RNA Pol II binding and downregulation of genes involved in estrogen signaling, cell cycle and stem cell pathways associated with CTx-648 anti-tumor activity in ER-positive (ER+) breast cancer. CTx-648 treatment leads to potent tumor growth inhibition in ER+ breast cancer in vivo models, including models refractory to endocrine therapy, highlighting the potential for targeting KAT6A in ER+ breast cancer.

2023-06-05 | GSE233784 | GEO

Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [RNA-Seq]

2023-06-05 | GSE233783 | GEO

Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [BrU-Seq]

2023-06-05 | GSE233787 | GEO

Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [ChIP-Seq - CUT&RUN]

2023-06-05 | GSE233788 | GEO

Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363

Project description:Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363

| PRJNA977979 | ENA

Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [ATAC-Seq]

Project description:Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [ATAC-Seq]

| PRJNA977984 | ENA

Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [BrU-Seq]

Project description:Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [BrU-Seq]

| PRJNA977985 | ENA

Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [ChIP-Seq - CUT&RUN]

Project description:Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363 [ChIP-Seq - CUT&RUN]

| PRJNA977987 | ENA

Targeting KAT6A/KAT6B dependencies in breast cancer with a novel selective, orally bioavailable KAT6 inhibitor, CTx-648/PF-9363

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-06-05 | GSE233789 | GEO

Identification of KAT6B signature on KAT6B deficient SCLC cell Lines

Project description:To develop our gene expression experiment, we have employed whole genome microarray expression profiling as a discovery platform to identify genes potentially regulated by the transcriptional coactivator KAT6B. Expression of KAT6B gene was downregulated in two human SCLC cell lines using two different short hairpin RNAs. RNAs from these modified cell lines were hybridized in Agilent platform.

2015-10-07 | GSE59136 | GEO

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