THAL-SNS-032 is a selective CDK9 degrader consisting of a CDK-binding SNS-032 ligand linked to a thalidomide derivative which binds the E3 ubiquitin ligase Cereblon (CRBN). THAL-SNS-032 induces rapid degradation of CDK9 without affecting the levels of other SNS-032 targets. The transcriptional changes elicited by THAL-SNS-032 are more like those caused by NVP-2 than those induced by SNS-032. Strikingly, compound washout does not significantly reduce levels of THAL-SNS-032-induced apoptosis, suggesting that CDK9 degradation had prolonged cytotoxic effects compared to CDK9 inhibition.
