BI 9811

BI 9811 is a potent and selective small molecule inhibitor of cyclin-dependent kinase 8 (CDK8), developed by Boehringer Ingelheim. CDK8 is a component of the mediator complex that regulates transcription, specifically by phosphorylating signal transducer and activator of transcription 1 (STAT1) at the Ser727 position. By inhibiting CDK8, BI 9811 reduces pSTAT1-Ser727 levels, which has been shown to enhance natural killer (NK) cell cytotoxicity and increase the secretion of effector molecules such as perforin and granzyme B. This mechanism is intended to leverage the immune system for improved tumor surveillance and anti-tumor activity. In preclinical studies, BI 9811 and related compounds have demonstrated biomarker modulation and survival benefits in melanoma models.