Virtual screening of the Cyclin-dependent kinase library for the identification of potential CDK11 inhibitors

Abstract

Cancer remains one of the leading causes of death worldwide, emphasizing the need for the development of more specific and potent treatment strategies, as existing therapies are often accompanied by a high toxicity profile, including drug resistance and off-target effects. The cyclin-dependent kinase 11 (CDK11), a crucial regulator of cell cycle progression and transcription, is frequently overexpressed in multiple cancers and is associated with poor prognosis. This study aims to identify potential CDK11 inhibitors through an in silico analysis. A ligand-based virtual screening was conducted against 1,000 compounds sourced from a kinase-focused library; the binding affinities of the best compounds were compared with the existing inhibitor OTS964 as the standard. Top candidates were further assessed for pharmacokinetic properties, drug-likeness, and toxicity through ADMET analysis. Several compounds demonstrated stronger binding interactions with the CDK11 active site than the standard and exhibited favorable pharmacological profiles. These findings propose promising hit molecules for subsequent in vitro and in vivo validation, contributing to the development of more precise and effective targeted anti-cancer therapies.