CDK8 as a therapeutic target for cancers and recent developments in discovery of CDK8 inhibitors.
Sign Up to like & getrecommendations! Published in 2019 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2018.11.076
Abstract: Cyclin-dependent kinases 8 (CDK8) regulates transcriptional process via associating with the mediator complex or phosphorylating transcription factors (TF). Overexpression of CDK8 has been observed in various cancers. It mediates aberrant activation of Wnt/β-catenin signaling pathway,… read more here.
Keywords: cdk8 inhibitors; cdk8 therapeutic; cdk8; cancers recent ... See more keywords
Discovery of a potent, highly selective, and orally bioavailable inhibitor of CDK8 through a structure-based optimisation.
Sign Up to like & getrecommendations! Published in 2021 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2021.113391
Abstract: CDK8 is deregulated in multiple types of human cancer and is viewed as a therapeutic target for the treatment of the disease. Accordingly, the search for small-molecule inhibitors of CDK8 is being intensified. Capitalising on… read more here.
Keywords: inhibitor; based optimisation; cdk8; structure based ... See more keywords
In Search of Novel CDK8 Inhibitors by Virtual Screening
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DOI: 10.1021/acs.jcim.6b00711
Abstract: Aberrant activity of cyclin-dependent kinase (CDK) 8 is implicated in various cancers. While CDK8-targeting anticancer drugs are highly sought-after, no CDK8 inhibitor has yet reached clinical trials. Herein a large library of drug-like molecules was… read more here.
Keywords: virtual screening; cdk8 inhibitors; search novel; cdk8 ... See more keywords
Discovery and Anti-Inflammatory Activity Evaluation of a Novel CDK8 Inhibitor through Upregulation of IL-10 for the Treatment of Inflammatory Bowel Disease In Vivo.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c00356
Abstract: Increasing the anti-inflammatory cytokine interleukin-10 (IL-10) level is a promising strategy to suppress the progression of pathogenic inflammation including inflammatory bowel disease (IBD). Since cyclin-dependent kinase 8 (CDK8) inhibition can upregulate IL-10 abundance in activated… read more here.
Keywords: cdk8 inhibitor; inflammatory bowel; cdk8; anti inflammatory ... See more keywords
Design and Synthesis of a 2-Amino-pyridine Derivative as a Potent CDK8 Inhibitor for Anti-colorectal Cancer Therapy.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c01042
Abstract: CDK8 is a transcriptional cyclin-dependent kinase and considered as a potential target in colon cancer therapeutics. Here, a novel selective CDK8 inhibitor was identified against colon cancer in vivo. Specifically, based on the structural information… read more here.
Keywords: cdk8 inhibitor; cdk8; colon cancer; cancer ... See more keywords
Small-molecule studies identify CDK8 as a regulator of IL-10 in myeloid cells.
Sign Up to like & getrecommendations! Published in 2017 at "Nature chemical biology"
DOI: 10.1038/nchembio.2458
Abstract: Enhancing production of the anti-inflammatory cytokine interleukin-10 (IL-10) is a promising strategy to suppress pathogenic inflammation. To identify new mechanisms regulating IL-10 production, we conducted a phenotypic screen for small molecules that enhance IL-10 secretion… read more here.
Keywords: identify cdk8; small molecule; cdk8 cdk19; cdk8 ... See more keywords
Mediator kinase CDK8/CDK19 drives YAP1-dependent BMP4-induced EMT in cancer
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DOI: 10.1038/s41388-018-0316-y
Abstract: CDK8 is a transcription-regulating kinase that controls TGF-β/BMP-responsive SMAD transcriptional activation and turnover through YAP1 recruitment. However, how the CDK8/YAP1 pathway influences SMAD1 response in cancer remains unclear. Here we report that SMAD1-driven epithelial-to-mesenchymal transition… read more here.
Keywords: mediator kinase; cdk19; cdk8; cancer ... See more keywords
A kinase-independent role for CDK8 in BCR-ABL1+ leukemia
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DOI: 10.1038/s41467-019-12656-x
Abstract: Cyclin-dependent kinases (CDKs) are frequently deregulated in cancer and represent promising drug targets. We provide evidence that CDK8 has a key role in B-ALL. Loss of CDK8 in leukemia mouse models significantly enhances disease latency… read more here.
Keywords: abl1 leukemia; cdk8; mtor; role ... See more keywords
Inhibition of CDK8/19 Mediator kinase potentiates HER2-targeting drugs and bypasses resistance to these agents in vitro and in vivo
Sign Up to like & getrecommendations! Published in 2022 at "Proceedings of the National Academy of Sciences of the United States of America"
DOI: 10.1073/pnas.2201073119
Abstract: Significance Breast cancers that overexpress oncogenic tyrosine kinase receptor HER2 are treated with HER2-targeting antibodies (such as trastuzumab) or small-molecule kinase inhibitors (such as lapatinib). However, most patients with metastatic HER2+ breast cancer have intrinsic… read more here.
Keywords: kinase; her2 targeting; cdk8; resistance ... See more keywords
Abstract A187: Exploring isoform-dependent functions of the mediator kinases in colorectal cancer
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DOI: 10.1158/1535-7163.targ-17-a187
Abstract: Introduction: CDK8 and its paralogue CDK19 are highly similar cyclin-dependent kinases that function as components of the kinase module of the Mediator complex. Despite their structural similarity, emerging data suggest that these proteins may have… read more here.
Keywords: transcription; isoform dependent; dependent functions; colorectal cancer ... See more keywords
Abstract 4896: Role of CDK8 in colon cancer hepatic metastasis
Sign Up to like & getrecommendations! Published in 2017 at "Cancer Research"
DOI: 10.1158/1538-7445.am2017-4896
Abstract: About half of all colon cancer patients will develop liver metastases and the 5-year survival for these patients is less than 13%, making colon cancer the second most lethal cancer worldwide. Cyclin dependent kinase 8… read more here.
Keywords: hepatic metastasis; metastasis; cdk8; colon cancer ... See more keywords