Respones to treatment of H209 and H838 cell lines to treatment with the non-covalent inhibitor of TRXR1, DKFZ-608
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ABSTRACT:
PROVIDER: PRJNA508383 | ENA |
REPOSITORIES: ENA
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Project description:DKFZ-608 induces oxidative stress in the cytoplasm of treated cancer cell lines. The molecular reason for this is the inhibition of the cytoplamic thioredoxin reductase TRXR1. The EC50 of cytotoxicity differes substantialy in SCLC (hypersensitive) and NSCLC (resistant). The experiment aims to identify stress response pathways induced by the compound which could explain the cytotoxic activity of the compound and its differential effect.
2019-12-02 | GSE123340 | GEO
Project description:The expression level of miR-608 was found to be down regulated in several types of cancer. In our previous study, a single SNP in miR-608 (rs4919510) was found to be strongly associated with a higher risk of developing sepsis and multiple organ dysfunctions in all 3 independent study cohorts. However, the clinicopathological impact and the exact roles of miR-608 and its underlying molecular mechanisms in inflammation remain to be identified. In order to identify the exact terget gene of miR-608 in monocytes, we constructed lentiviral vectors with has-miR-608 inhibitor sequences and transfected U937 cells.We used microarrays to identified distinct classes of up-regulated genes during this process and look for possible target genes. U937 cells transfected by has-miR-608 inhibitor lentiviral vectors or negative control virus were analyzed. There are three samples in each group.
2015-12-12 | E-GEOD-75911 | biostudies-arrayexpress
Project description:The expression level of miR-608 was found to be down regulated in several types of cancer. In our previous study, a single SNP in miR-608 (rs4919510) was found to be strongly associated with a higher risk of developing sepsis and multiple organ dysfunctions in all 3 independent study cohorts. However, the clinicopathological impact and the exact roles of miR-608 and its underlying molecular mechanisms in inflammation remain to be identified. In order to identify the exact terget gene of miR-608 in monocytes, we constructed lentiviral vectors with has-miR-608 inhibitor sequences and transfected U937 cells.We used microarrays to identified distinct classes of up-regulated genes during this process and look for possible target genes.
2015-12-12 | GSE75911 | GEO
Project description:SY-1365, a covalent, first in-class CDK7 inhibitor for cancer treatment
| PRJNA497304 | ENA
Project description:SY-1365, a covalent, first in-class CDK7 inhibitor for cancer treatment (microarray mRNA)
| PRJNA496593 | ENA
Project description:SY-1365, a covalent, first in-class CDK7 inhibitor for cancer treatment (ChIP-Seq)
| PRJNA497305 | ENA
Project description: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. Cancer cell line profiling indicates that a subset of cancer cell lines, including T-cell acute lymphoblastic leukemia (T-ALL), exhibit 100-fold greater sensitivity to CDK7-IN-1 over other tumor and normal cell lines. Genome-wide expression analysis in Jurkat T-ALL indicates that CDK7-IN-1 disproportionally affects RUNX1 as well as other components of the TAL1 transcriptional network and its targets, downregulating key regulators of transcription and apoptosis critical for the T-ALL state. These oncogenes are encoded by short-lived mRNA transcripts, are associated with super-enhancers, and exhibit a strong dependency on continuous transcription for sustained expression. Therefore, pharmacological modulation of CDK7 kinase activity may define a method for the identification and treatment of tumor types exhibiting extreme dependencies on transcription for maintenance of the oncogenic state. Jurkat, MM1S, Loucy, and HeLa (WT and Dox-inducible CDK7 mutant) cells were treated with various drugs including a covalent inhibitor of CDK7 (CDK7-IN-1), a reversible inhibitor of CDK7 (CDK7-IN-1), Flavopiridol, Actinomycin D, and DMSO controls. Replicates are annotated.
2014-06-22 | E-GEOD-50624 | biostudies-arrayexpress
Project description: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. Cancer cell line profiling indicates that a subset of cancer cell lines, including T-cell acute lymphoblastic leukemia (T-ALL), exhibit 100-fold greater sensitivity to CDK7-IN-1 over other tumor and normal cell lines. Genome-wide expression analysis in Jurkat T-ALL indicates that CDK7-IN-1 disproportionally affects RUNX1 as well as other components of the TAL1 transcriptional network and its targets, downregulating key regulators of transcription and apoptosis critical for the T-ALL state. These oncogenes are encoded by short-lived mRNA transcripts, are associated with super-enhancers, and exhibit a strong dependency on continuous transcription for sustained expression. Therefore, pharmacological modulation of CDK7 kinase activity may define a method for the identification and treatment of tumor types exhibiting extreme dependencies on transcription for maintenance of the oncogenic state. Jurkat cells were treated with various drugs including a covalent inhibitor of CDK7 (CDK7-IN-1), a reversible inhibitor of CDK7 (CDK7-IN-1), Flavopiridol, Actinomycin D, and DMSO controls. Replicates are annotated.
2013-12-23 | E-GEOD-50622 | biostudies-arrayexpress
Project description:Small cell lung cancer (SCLC) is an aggressive disease with high mortality. The identification of effective pharmacological strategies to target SCLC biology represents an urgent need. Using a high-throughput cellular screen of a diverse chemical library we observe that SCLC is sensitive to transcription-targeting drugs, and in particular to THZ1, a newly identified covalent inhibitor of cyclin-dependent kinase 7 (CDK7). We find that expression of super-enhancer associated transcription factor genes including MYC family proto-oncogenes and neuroendocrine lineage-specific factors are highly vulnerability to THZ1 treatment. We propose that downregulation of these transcription factors contributes, in part, to SCLC sensitivity to transcriptional inhibitors and that THZ1 represents a novel treatment paradigm for targeted SCLC therapy. Microarray expression in small cell lung cancer lines treated with DMSO or THZ1
2014-10-23 | E-GEOD-62609 | biostudies-arrayexpress
Project description:A Phase 1/1b dose finding study to determine the OBD(s) and RP2D(s) of BMF-219, a covalent menin inhibitor small molecule, in subjects with KRAS mutated unresectable, locally advanced, or metastatic NSCLC (Cohort 1), PDAC (Cohort 2), and CRC (Cohort 3).
| 919 | ecrin-mdr-crc