TGN-1069

TGN-1069 is a novel, orally available, selective, and reversible small molecule inhibitor of cyclin-dependent kinase 7 (CDK7). Developed by the Translational Genomics Research Institute (TGen), it was identified through fragment-based screening and optimization of the TGN-1062 series. CDK7 is a critical regulator of the transcriptional machinery, specifically initiating transcription by phosphorylating the C-terminal domain of RNA polymerase II, which drives the expression of oncogenic super-enhancers like Myc. TGN-1069 has demonstrated high potency against CDK7 (IC50 = 38 nM) with significant selectivity over other CDKs such as CDK2 and CDK5. Preclinical studies in pancreatic cancer models have shown that TGN-1069 suppresses RNA Pol II phosphorylation and c-Myc expression, leading to reduced cell viability and efficacy in vivo.