Tandutinib hydrochloride

Tandutinib is a potent antagonist of platelet-derived growth factor receptor β (PDGFRβ), FLT3, and c-Kit (IC₅₀ = 200, 220, and 170 nM, respectively).¹ It less potently inhibits macrophage colony-stimulating factor 1 receptor (IC₅₀ = 3.4 ?M) and does not significantly inhibit other tyrosine or serine/threonine kinases.^1,2 Tandutinib blocks the growth of cells expressing an internal tandem duplication within the juxtamembrane domain of the FLT3 receptor, found in some acute myelogenous leukemia cells.^1,3 It also impairs the growth of colon cancer cells through its actions on the c-Kit receptor.⁴ Tandutinib reverses multidrug resistance in vitro by impairing the efflux activity of the multidrug resistance protein 7.⁵

1.Kelly, L.M., Yu, J.C., Boulton, C.L., et al.CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML)Cancer Cell.1(5)421-432(2002) 2.Pandey, A., Volkots, D.L., Seroogy, J.M., et al.Identification of orally active, potent, and selective 4-piperazinylquinazolines as antagonists of the platelet-derived growth factor receptor tyrosine kinase familyJ. Med. Chem.45(17)3772-3793(2002) 3.Griswold, I.J., Shen, L.J., La Rosée, P., et al.Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesisBlood104(9)2912-2918(2004) 4.Ponnurangam, S., Standing, D., Rangarajan, P., et al.Tandutinib inhibits the Akt/mTOR signaling pathway to inhibit colon cancer growthMol. Cancer Ther.12(5)598-609(2013) 5.Deng, W., Dai, C.L., Chen, J.J., et al.Tandutinib (MLN518) reverses multidrug resistance by inhibiting the efflux activity of the multidrug resistance protein 7 (ABCC10)Oncol. Rep.29(6)2479-2485(2013)