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Drug Discovery from Mother Nature pp 209–228Cite as

Potential Use of Flavopiridol in Treatment of Chronic Diseases

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 929))

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.

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Acknowledgments

The work in JP’s laboratory is supported by funds from Anna Valentine Moffitt/USF Collaborative Grant and Small Grant Program from USF Health Byrd Alzheimer’s Institute.

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Authors and Affiliations

  1. Morsani College of Medicine, University of South Florida, Tampa, Florida, 33612, USA

    Thejal Srikumar

  2. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, 33612, USA

    Jaya Padmanabhan

  3. USF Health Byrd Alzheimer’s Institute, University of South Florida, 4001 E. Fletcher Ave., Tampa, Florida, 33613, USA

    Jaya Padmanabhan

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  1. Thejal Srikumar
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  2. Jaya Padmanabhan
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Correspondence to Jaya Padmanabhan .

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Editors and Affiliations

  1. Banaras Hindu University, Varanasi, Uttar Pradesh, India

    Subash Chandra Gupta

  2. MD Anderson Cancer Center, University of Texas, Houston, Texas, USA

    Sahdeo Prasad

  3. Inflammation Research Institute, San Diego, California, USA

    Bharat B. Aggarwal

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Srikumar, T., Padmanabhan, J. (2016). Potential Use of Flavopiridol in Treatment of Chronic Diseases. In: Gupta, S., Prasad, S., Aggarwal, B. (eds) Drug Discovery from Mother Nature. Advances in Experimental Medicine and Biology, vol 929. Springer, Cham. https://doi.org/10.1007/978-3-319-41342-6_9

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