- Guide to PHARMACOLOGY
Compound class: Synthetic organic
Comment: This compound is a novel and selective cyclin-dependent kinase 12 (CDK12) and CDK13 inhibitor . It is a chemical probe that is suitable for functional studies of CDK12, and a scaffold for further drug discovery efforts. CDK12 is an oncology drug target as its inhibition sensitises cancer cells to DNA-damaging reagents and DNA-repair inhibitors. The chemical structure was generated from the SMILES string supplied with the original J Med Chem article by Ito et al. (2018) .
Ligand Activity Visualisation Charts
These 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.✖
|This kinase inhibitor (2) is selective for CDK12/13 over other related C-terminal domain kinases. In a kinome wide-selectivity screen only TAOK1, DYRK2, and STK39 were inhibited by >80% at 1 μM compound. As these kinases play no functional roles in splicing or RNA processing, their inhibition by this compound is unlikely to impact analysis of its use in the investigation of RNA biology. Functional efficacy of inhibitor 2 was demonstrated in vitro by its ability to reduce phosphorylation of RNA polymerase II at its C-terminal domain Ser2 residue in SK-BR-3 cells and to inhibit cell growth .|
|Selectivity at enzymes|
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