alvocidib and Chronic-Disease

This chapter describes the potential use of flavopiridol, a CDK inhibitor with anti-inflammatory and anti-proliferative activities, in the treatment of various chronic diseases. Flavopiridol arrests cell cycle progression in the G1 or G2 phase by inhibiting the kinase activities of CDK1, CDK2, CDK4/6, and CDK7. Additionally, it binds tightly to CDK9, a component of the P-TEFb complex (CDK9/cyclin T), and interferes with RNA polymerase II activation and associated transcription. This in turn inhibits expression of several pro-survival and anti-apoptotic genes, and enhances cytotoxicity in transformed cells or differentiation in growth-arrested cells. Recent studies indicate that flavopiridol elicits anti-inflammatory activity via CDK9 and NFκB-dependent signaling. Overall, these effects of flavopiridol potentiate its ability to overcome aberrant cell cycle activation and/or inflammatory stimuli, which are mediators of various chronic diseases.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Antiviral Agents; Apoptosis; Cardiovascular Agents; Cell Cycle Checkpoints; Cell Proliferation; Chronic Disease; Disease Models, Animal; Drug Discovery; Flavonoids; Humans; Molecular Structure; Phytotherapy; Piperidines; Plants, Medicinal; Signal Transduction