Targeting CDK9 in Cancer: An Integrated Approach of Combining In Silico Screening with Experimental Validation for Novel Degraders.

ABSTRACT

The persistent threat of cancer remains a significant hurdle for global health, prompting the exploration of innovative approaches in the quest for successful therapeutic interventions. Cyclin-dependent kinase 9 (CDK9), a central player in transcription regulation and cell cycle progression, has emerged as a promising target to combat cancer. Its pivotal role in oncogenic pathways and the pressing need for novel cancer treatments has propelled CDK9 into the spotlight of drug discovery efforts. This article presents a comprehensive study that connects a multidisciplinary approach, combining computational methodologies, experimental validation, and the transformative Proteolysis-Targeting Chimera (PROTAC) technology. By uniting these diverse techniques, we aim to identify, characterize, and optimize a new class of degraders targeting CDK9. We explore these compounds for targeted protein degradation, offering a novel and potentially effective approach to cancer therapy. This cohesive strategy utilizes the combination of computational predictions and experimental insights, with the goal of advancing the development of effective anticancer therapeutics, targeting CDK9.