GEO DataSets

(Submitter supplied) Purpose: To assess THZ1-induced global changes of transcriptome of Hh-driven cancer Methods: SMB56 or SMB56-shSufu cells were mouse hedgehog-driven medulloblastoma cell lines that are either responsive or resistant to SMO inhibitor (GDC-0449). They were treated with 0.1 uM THZ1 or DMSO for 8 hours. 1 uM GDC-0449 treated SMB56 cells were included as control. Gene expression profiles were generated by RNAseq, in duplicate, using Hiseq3000. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL21273 GPL21493

10 Samples

Download data: XLSX

(Submitter supplied) THZ1 inhibits cancer stemness via Hedgehog pathway.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

2 Samples

Download data: TXT, XLSX

(Submitter supplied) Gene expression profiling were examined by Human HT-12 v4.0 Expression BeadChip arrays in SKBR3 and BT474 cells treated with HER2 inhibitor lapatinib or CDK7 inhibitor THZ1.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

18 Samples

Download data: IDAT

(Submitter supplied) Transcriptomic changes were compared by RNA-seq in human mammary epithelial cells (HMECs) with or without ectopic expression of oncogenic kinase HER2, PI3KCA(mut), or SHP(mut).

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: TXT

(Submitter supplied) Peripheral T-cell lymphomas (PTCL) are aggressive diseases with poor response to chemotherapy and dismal survival. Identification of effective strategies to target PTCL biology represents an urgent need. Here we report that PTCL are sensitive to transcription-targeting drugs, and, in particular, to THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7). The STAT-signaling pathway is highly vulnerable to THZ1 even in PTCL cells that carry the activating STAT3 mutation Y640F. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: TXT

(Submitter supplied) By screening an epigenetic-related compound library, we identified THZ1, a covalent inhibitor of CDK7, as a promising candidate. Multiple long-established and patient-derived PDAC cell lines (PDC) were used to validate the efficacy of THZ1 in vitro. In addition, patient-derived xenograft (PDX) models and animal models of PDAC were utilized for examining THZ1 efficacy in vivo. Furthermore, RNA-Seq and H3K27Ac-based Super-Enhancers (SEs) analyses were performed to reveal the molecular mechanism of THZ1 treatment. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20795

18 Samples

Download data: TXT

(Submitter supplied) Comparison of gene expression changes in Ptch-deficient mouse medulloblastoma cell line SmoWT-MB upon treatment with SMOi GDC-0449 or BETi JQ1. The hypothesis is that they can both inhibit the expressions of Hh signaling target genes in this Hh-driven tumor cell line.

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL18752

6 Samples

Download data: TXT

(Submitter supplied) Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric brain tumor with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone 3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using either bromodomain inhibition or CDK7 blockade. We observe that targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition and that DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL20301 GPL18573

26 Samples

Download data: BW, TXT

(Submitter supplied) ZNF521 is a transcription co-factor with recognized regulatory functions in haematopoietic, osteo-adipogenic and neural progenitor cells. Among its diverse activities, ZNF521 has been implicated in the regulation of medulloblastoma (MB) cells, where the Hedgehog (HH) pathway, has a key role in the development of normal cerebellum and of a substantial fraction of MBs. Here a functional cross-talk is shown for ZNF521 with the HH pathway, where it interacts with GLI1 and GLI2, the major HH transcriptional effectors and enhances the activity of HH signalling. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

4 Samples

Download data: TXT

(Submitter supplied) Cdk7, the CDK-activating kinase and transcription factor IIH component, is a target of inhibitors that kill cancer cells by exploiting tumor-specific transcriptional dependencies. However, whereas selective inhibition of analog-sensitive (AS) Cdk7 in colon cancer derived cells arrests division and disrupts transcription, it does not by itself trigger apoptosis efficiently. Here we show that p53 activation by 5-fluorouracil or nutlin-3 synergizes with a reversible Cdk7as inhibitor to induce cell death. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

8 Samples

Download data: TXT

(Submitter supplied) Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancy and accounts for the majority of thyroid cancer-related deaths. Despite intensive research, there remains no effective treatment for patients with ATC. Here, we identify THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), as a potent anti-ATC compound by high-throughput chemical screening. ATC cells, but not papillary thyroid cancer (PTC) cells, are exceptionally sensitive to CDK7 inhibition. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL23227

12 Samples

Download data: TXT

(Submitter supplied) Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancy and accounts for the majority of thyroid cancer-related deaths. Despite intensive research, there remains no effective treatment for patients with ATC. Here, we identify THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), as a potent anti-ATC compound by high-throughput chemical screening. ATC cells, but not papillary thyroid cancer (PTC) cells, are exceptionally sensitive to CDK7 inhibition. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL23227

8 Samples

Download data: TXT

(Submitter supplied) Anaplastic thyroid carcinoma (ATC) is one of the most aggressive malignancy and accounts for the majority of thyroid cancer-related deaths. Despite intensive research, there remains no effective treatment for patients with ATC. Here, we identify THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), as a potent anti-ATC compound by high-throughput chemical screening. ATC cells, but not papillary thyroid cancer (PTC) cells, are exceptionally sensitive to CDK7 inhibition. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL23227

4 Samples

Download data: WIG

(Submitter supplied) The CDK7 inhibitor THZ1 has been shown to suppress MYCN gene transcription but not cause significant cell death as a single agent. The tyrosine kinase inhibitors (TKIs) ponatinib and lapatinib were found to exert synergistic anti-cancer effects in combination with the CDK7 inhibitor THZ1, on MYCN amplified neuroblastoma cell lines.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16686

6 Samples

Download data: CEL, XLSX

(Submitter supplied) Identifying a mechanism by which CDK7 inhibitor resistance occurs in TNBC

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL16043 GPL11154 GPL9115

92 Samples

Download data: CEL, CHP, WIG

(Submitter supplied) Cyclin-dependent kinase 7 (CDK7) plays a critical role in the general regulation of RNA polymerase II-mediated transcription. However, the absence of selective CDK7 inhibitors has hindered the ability to investigate the consequences of acute and prolonged inhibition of CDK7 under normal and pathological conditions. Here we present the discovery and characterization of the first covalent CDK7 inhibitor, CDK7-IN-1, that has the unprecedented ability to target a unique cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7 amongst the 20 known CDKs. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16043

79 Samples

Download data: CEL, CHP

(Submitter supplied) Cyclin-dependent kinase 7 (CDK7) plays a critical role in the general regulation of RNA polymerase II-mediated transcription. However, the absence of selective CDK7 inhibitors has hindered the ability to investigate the consequences of acute and prolonged inhibition of CDK7 under normal and pathological conditions. Here we present the discovery and characterization of the first covalent CDK7 inhibitor, CDK7-IN-1, that has the unprecedented ability to target a unique cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7 amongst the 20 known CDKs. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL9115 GPL11154

13 Samples

Download data: WIG

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platform:

GPL11154

16 Samples

Download data: BW, TXT

(Submitter supplied) Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy and the major histological subtype of esophageal cancer. Although recent large-scale genomic analysis has improved the description of the genetic abnormalities of ESCC, few targetable genomic lesions were identified and no molecular-based therapy is available. To identify druggable candidates in this tumor, we performed high-throughput small-molecule inhibitor screening. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

12 Samples

Download data: TXT