Research Article Open Access
Volume 2 | Issue 2 | DOI: https://doi.org/10.33696/haematology.2.028

Flavopiridol (Alvocidib), a Cyclin-dependent Kinases (CDKs) Inhibitor, Found Synergy Effects with Niclosamide in Cutaneous T-cell Lymphoma

  • 1Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Beckman Research Institute, National Medical Center, Duarte, CA 91010, USA
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Corresponding Author

Xu Hannah Zhang, xuzhang@coh.org

Steven T. Rosen, srosen@coh.org

Received Date: April 14, 2021

Accepted Date: May 04, 2021


Flavopiridol (FVP; Alvocidib), a CDKs inhibitor, is currently undergoing clinical trials for treatment of leukemia and other blood cancers. Our studies demonstrated that FVP also inhibited p38 kinases activities with IC50 (µM) for p38a: 1.34; p38 ß: 1.82; p38α: 0.65, and p38d: 0.45. FVP showed potent cytotoxicity in cutaneous T-cell lymphoma (CTCL) Hut78 cells, with IC50 <100 nM. NMR analysis revealed that FVP bound to p38α in the ATP binding pocket, causing allosteric perturbation from sites surrounding the ATP binding pocket. Kinomic profiling with the PamGene platform in both cell-based and cell-free analysis further revealed dosage of FVP significantly affects downstream pathways in treated CTCL cells, which suggested a need for development of synergistic drugs with FVP to prevent its clinically adverse effects. It led us discover niclosamide as a synergistic drug of FVP for our future in vivo study.


Flavopiridol, p38γ, ATP binding pocket, NF-κB pathway, PamGene platform, Kinomic profiling, Development of synergistic drug

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