Compound class:
Synthetic organic
Comment: Compound 51 is a potent and selective CDK8/19 inhibitor [3]. It is one of the compounds claimed in patent WO2016009076 [4]. Compound 51 hasa similar inhibitory potency as CCT251545, but is built on a modified chemical scaffold [3]. This is a type I inhibitor, binding in a DMG-in mode.
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
|
No information available. |
Mechanism Of Action and Pharmacodynamic Effects |
CDK8, and its closely related isoform CDK19, are oncogenic transcription-regulating kinases. CDK8 depletion does not inhibit the growth of normal cells. CDK8 is a regulator of several transcriptional programs involved in carcinogenesis (such as the Wnt/β-catenin and TGFβ signaling pathways). CDK8 is reported to be oncogenic in melanoma [2] and colon cancers [1]. CDK8 is upregulated and amplified in a subset of human colon tumours and is required for colon cancer proliferation in vitro. Inhibitors of CDK8/19 are therefore being developed for use in oncology. |