Definition

An orally bioavailable, small-molecule cyclin-dependent kinase (CDK) inhibitor with potential proapoptotic and antineoplastic activities. Seliciclib primarily inhibits CDK2/E, CDK2/A, CDK7 and CDK9 by competing for their ATP binding sites, leading to a disruption of cell cycle progression. In addition, this agent appears to interfere with CDK-mediated phosphorylation of the carboxy-terminal domain of RNA polymerase II, inhibiting RNA polymerase II-dependent transcription, which may result in the down-regulation of antiapoptotic proteins such as induced myeloid leukemia cell differentiation protein Mcl-1. CDKs, serine/threonine kinases that play an important role in cell cycle regulation, are overexpressed in various malignancies. Mcl-1 belongs to the Bcl-2 family of antiapoptotic proteins and is a protein crucial to the survival of a range of tumor cell types.