title: Potential Use of Flavopiridol in Treatment of Chronic Diseases.
abstract: 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.
authors: Morsani College of Medicine, University of South Florida, Tampa, Florida, 33612, USA.
authors: Thejal
authors: T
authors: Srikumar
authors: Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, 33612, USA. jpadmana@health.usf.edu.|USF Health Byrd Alzheimer's Institute, University of South Florida, 4001 E. Fletcher Ave., Tampa, Florida, 33613, USA. jpadmana@health.usf.edu.
authors: Jaya
authors: J
authors: Padmanabhan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002317:Cardiovascular Agents / Q000737:chemistry / Q000627:therapeutic use*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002908:Chronic Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000379:methods*; D005419:Flavonoids / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D015394:Molecular Structure; D008517:Phytotherapy; D010880:Piperidines / Q000737:chemistry / Q000627:therapeutic use*; D010946:Plants, Medicinal; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D000998:Antiviral Agents; D002317:Cardiovascular Agents; D005419:Flavonoids; D010880:Piperidines; C077990:alvocidib
keywords: CDKs; Coronary heart disease; Flavopiridol; Hematologic malignancies; Infectious disease; Inflammation; Neurodegenerative diseases; Solid tumors