Flavopiridol is obtained from a synthetic process, but its chemical structure is identical to a product obtained from an indigenous plant in India called Dysoxylum binectariferum. When flavopiridol was first discovered, it was considered to be a tyrosine kinase antagonist but subsequently, it was shown to reversibly inhibit growth via inhibition of cyclin-dependent kinase (CDK)1 and CDK2[1, 2]. Flavopiridol induced cell cycle inhibition by altering phosphorylation of tyrosine residues as well as antagonizing CDK1 and CDK2 activity as a result of competitive inhibition with ATP[3]. Based on these initial observations, investigators hypothesized that flavopiridol would be effective in rapidly dividing tumor systems where a minimum volume of tumor exists. We now know that flavopiridol has a number of additional targets that include the cyclin D-1 complex over-expressed in mantle cell lymphoma and cyclin H. In addition, studies in lymphoma cell lines have demonstrated activity against activated B-cell (ABC) type cell lines and NF-kappa B down-regulation[4, 5].

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIABC010715-08
Application #
8763184
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2013
Total Cost
$100,298
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Dunleavy, Kieron; Roschewski, Mark; Wilson, Wyndham H (2012) Lymphomatoid granulomatosis and other Epstein-Barr virus associated lymphoproliferative processes. Curr Hematol Malig Rep 7:208-15
Wilson, Wyndham H; Jung, Sin-Ho; Porcu, Pierluigi et al. (2012) A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype. Haematologica 97:758-65
Degheidy, Heba A; Venzon, David J; Farooqui, Mohammed Z H et al. (2012) Combined normal donor and CLL: Single tube ZAP-70 analysis. Cytometry B Clin Cytom 82:67-77
Royo, C; Navarro, A; Clot, G et al. (2012) Non-nodal type of mantle cell lymphoma is a specific biological and clinical subgroup of the disease. Leukemia 26:1895-8
Roschewski, Mark; Wilson, Wyndham H (2012) EBV-associated lymphomas in adults. Best Pract Res Clin Haematol 25:75-89
Dunleavy, Kieron; Grant, Cliona; Eberle, Franziska C et al. (2012) Gray zone lymphoma: better treated like hodgkin lymphoma or mediastinal large B-cell lymphoma? Curr Hematol Malig Rep 7:241-7
Eberle, Franziska C; Song, Joo Y; Xi, Liqiang et al. (2012) Nodal involvement by cutaneous CD30-positive T-cell lymphoma mimicking classical Hodgkin lymphoma. Am J Surg Pathol 36:716-25
Dunleavy, Kieron; Wilson, Wyndham H (2012) How I treat HIV-associated lymphoma. Blood 119:3245-55
Eberle, Franziska C; Salaverria, Itziar; Steidl, Christian et al. (2011) Gray zone lymphoma: chromosomal aberrations with immunophenotypic and clinical correlations. Mod Pathol 24:1586-97
Degheidy, Heba A; Venzon, David J; Farooqui, Mohammed Z H et al. (2011) Methodological comparison of two anti-ZAP-70 antibodies. Cytometry B Clin Cytom 80:300-8

Showing the most recent 10 out of 21 publications