Compound class:
Synthetic organic
Comment: CP-10 is a selective CDK6 degrading PROTAC [1]. It is a bifunctional molecule that combines the CDK4/6 inhibitor palbociclib, with the cereblon ligand pomalidomide. The pomalidomide moiety recruits E3 ubiquitin ligase machinery to the palbociclib-bound kinase protein, which leads to proteasomal degradation of CDK6. Selectivity of CP-10 appears to be cell line dependent, so CDK4 levels should be monitored to detect off-target activity, given palbociclib's selectivity profile for CDK6 and CDK4. CP-10 degrades mutant forms of CDK6 (e.g. CDK6D163G) as efficiently as it degrades wild-type kinase protein, and it induces degradation of CDK6 and CDK4 and inhibits the proliferation in palbociclib resistant cell lines.
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. ✖ |
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References |
1. Su S, Yang Z, Gao H, Yang H, Zhu S, An Z, Wang J, Li Q, Chandarlapaty S, Deng H et al.. (2019)
Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders. J Med Chem, 62 (16): 7575-7582. [PMID:31330105] |