Ergosterol analogs as inhibitors of cyclin dependent kinase 8

Five new compounds based on the structure of ergosterol have been prepared and tested for their ability to inhibit CDK8. The design of the compounds was inspired by the previous reported CDK8 inhibitors, cortistatin A, CCT251921 and Senexin A. The two most potent compounds, 16a and 16d, inhibited the target enzyme with Kd-values of 107 and 93 nM, respectively.