RGB-344064

RGB-344064 is a potent, selective, and orally bioavailable small molecule inhibitor of Cyclin-Dependent Kinase 8 (CDK8) and its paralog CDK19, developed by Rigel Pharmaceuticals. These kinases are key components of the Mediator complex, which serves as a transcriptional co-activator bridging transcription factors to the RNA polymerase II machinery. CDK8 and CDK19 play critical roles in regulating gene expression programs associated with oncogenesis, including the Wnt/β-catenin, TGF-β, and hypoxic response pathways. By inhibiting these kinases, RGB-344064 aims to suppress the transcriptional reprogramming that drives tumor growth, metastasis, and resistance to conventional therapies. Preclinical studies have demonstrated its efficacy in various cancer models, particularly in solid tumors and hematological malignancies such as acute myeloid leukemia (AML).