Cyclin-dependent kinase 9 (CDK9), an essential regulator of transcriptional elongation, is really a promising target for cancer therapy, designed for cancers driven by transcriptional dysregulation. We characterised NVP-2, a selective ATP-competitive CDK9 inhibitor, and THAL-SNS-032, a selective CDK9 degrader composed of the CDK-binding SNS-032 ligand associated with a thalidomide derivative that binds the E3 ubiquitin ligase Cereblon (CRBN). To the surprise, THAL-SNS-032 caused rapid degradation of CDK9 without having affected the amount of other SNS-032 targets. Furthermore, the transcriptional changes elicited by THAL-SNS-032 were a lot more like individuals brought on by NVP-2 than individuals caused by SNS-032. Particularly, compound washout didn’t considerably reduce amounts of THAL-SNS-032-caused apoptosis, suggesting that CDK9 degradation had prolonged cytotoxic effects in contrast to CDK9 inhibition. Thus, our findings claim that thalidomide conjugation represents an encouraging technique for converting multi-targeted inhibitors into selective degraders and demonstrate that kinase degradation can induce distinct medicinal effects in contrast to inhibition.