SERP
Comments:
I would not view this chemical probe as of sufficient quality to interrogate consequences of CDK8 degradation in cells. No selectivity data is available for either the kinase binding selectivity or, more importantly, degradation selectivity across the proteome in relevant cell models. Most crucially, whilst effects observed are shown to be CRBN and proteasome dependent, there is no control to demonstrate that down regulation of CDK8 is dependent on the molecule binding to CDK8. It also appears that at the proposed concentrations only partially (not possible to assess how partial with current data set) reduce target protein levels, so some context as to why partial degradation would be of interest for functional investigation of the protein function would be ideal.
(last updated:
9 Mar 2022 )