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Compound class: Synthetic organic
Comment: CR8 is a small molecule inhibitor of cyclin-dependent kinases . It is structurally related to seliciclib (roscovitine). This entry is for the R isomer, which is more inhibitory at glycogen synthase kinase (GSK-3α/β) than the S isomer. Both isomers are equipotent across CDK1, 2, 5, 7, and 9.
(R)-CR8 has been shown to act as a molecular glue degrader that depletes cyclin K , thus behaving as a functional CDK inhibitor. (R)-CR8 binding to CDK12 induces formation of a complex between CDK12-cyclin K and the CUL4 adaptor protein DDB1 which presents cyclin K for ubiquitination and degradation. Of the >8,000 proteins assessed by quantitative proteome-wide mass spectrometry, cyclin K was the only one that was consistently decreased in abundance in response to (R)-CR8 exposure.
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.✖
1. Bettayeb K, Oumata N, Echalier A, Ferandin Y, Endicott JA, Galons H, Meijer L. (2008)
CR8, a potent and selective, roscovitine-derived inhibitor of cyclin-dependent kinases.
Oncogene, 27 (44): 5797-807. [PMID:18574471]
2. Słabicki M, Kozicka Z, Petzold G, Li YD, Manojkumar M, Bunker RD, Donovan KA, Sievers QL, Koeppel J, Suchyta D et al.. (2020)
The CDK inhibitor CR8 acts as a molecular glue degrader that depletes cyclin K.
Nature, 585 (7824): 293-297. [PMID:32494016]