Tandutinib  (Synonyms: MLN518; CT53518)

Tandutinib (MLN518) is a potent and selective inhibitor of the FLT3 with an IC₅₀ of 0.22 μM, and also inhibits c-Kit and PDGFR with IC₅₀s of 0.17 μM and 0.20 μM, respectively. Tandutinib can be used for acute myelogenous leukemia (AML)^[1][2]. Tandutinib has the ability to cross the blood-brain barrier^[3].

Tandutinib (0-3 μM; 30 minutes; Ba/F3 cells) treatment inhibits IL-3-independent cell growth and FLT3-ITD autophosphorylation with an IC₅₀ of 10-100 nM in Ba/F3 cells expressing different FLT3-ITD mutants^[1].
Tandutinib (1 μM; 24-96 hours; Molm-14 and THP-1 AML cells) treatment induces apoptosis in FLT3-ITD-positive AML cells^[1].
In human FLT3-ITD-positive AML cell lines, Tandutinib inhibits FLT3-ITD phosphorylation (IC₅₀ of ~30 nM). As with Erk2, a constitutively high level of Akt phosphorylation is readily detected and is efficiently blocked by pretreatment of the Molm-14 cells with 100-300 nM Tandutinib^[1].
Tandutinib inhibits cell proliferation of the FLT3-ITD-positive Molm-13 and Molm-14 with an IC₅₀ of 10 nM. And signaling through the MAP kinase and PI3 kinase pathways^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Tandutinib (60 mg/kg; oral gavage; daily; for 35 days; athymic nude mice) treatment causes a statistically significant increase in survival that was extended on average by 20 days^[1].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

562.70

Solid

C₃₁H₄₂N₆O₄

387867-13-2

O=C(N1CCN(C2=C(C(C=C3OCCCN4CCCCC4)=NC=N2)C=C3OC)CC1)NC5=CC=C(OC(C)C)C=C5

Room temperature in continental US; may vary elsewhere.

• [1]. Kelly LM, et al. CT53518, a novel selective FLT3 antagonist for the treatment of acute myelogenous leukemia (AML). Cancer Cell, 2002, 1(5), 421-432.  [Content Brief]

  [2]. Griswold IJ, et al. Effects of MLN518, a dual FLT3 and KIT inhibitor, on normal and malignant hematopoiesis. Blood, 2004, 104(9), 2912-2918.  [Content Brief]

  [3]. Yang JJ, et al. P-glycoprotein and breast cancer resistance protein affect disposition of tandutinib, a tyrosine kinase inhibitor. Drug Metab Lett. 2010 Dec;4(4):201-12.  [Content Brief]