Flavopiridol (Alvocidib), a Cyclin-dependent Kinases (CDKs) Inhibitor, Found Synergy Effects with Niclosamide in Cutaneous T-cell Lymphoma
Xu Hannah Zhang, Jack Hsiang, Steven T. Rosen
Abstract
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 p38?: 1.34; p38 ?: 1.82; p38?: 0.65, and p38?: 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 p38? in the ATP binding pocket, causing allosteric perturbation from sites surrounding the ATP binding pocket
Topics & Concepts
Cyclin-dependent kinaseAllosteric regulationCancer researchp38 mitogen-activated protein kinasesChemistryKinaseIC50LymphomaCDK inhibitorCytotoxicityBiochemistryMedicineCell cycleIn vitroCellEnzymeInternal medicineProtein kinase ACutaneous lymphoproliferative disorders researchChronic Lymphocytic Leukemia ResearchUbiquitin and proteasome pathways