Modulating Oncogenic Transcriptional Dysregulation with Small Molecule Degraders
CDK9 is an important co-factor for MYC, an oncogenic transcription factor known to drive transcription in an addictive manner. However, targeting CDK9 in the clinic has proven very challenging. Our recent development of a novel CDK9 inhibitor KI-ARv-03 and an analogous CDK9 PROTAC KI-ARv-03-D08 allows independent manipulation of the enzymatic and structural functionalities of CDK9 at fast time scales. The probes can be used to measure and model the immediate effects of CDK9 perturbation, facilitating the design of next-generation CDK9 probes that reduce toxicity and improve efficacy.