Tandutinib

SKU: orb1307840

Description

Tandutinib (MLN518) is a potent and selective FLT3 inhibitor (IC50 = 0.22 µM) with additional activity against c-Kit and PDGFR. It demonstrates significant selectivity over CSF-1R, FGFR, EGFR, and KDR. This small molecule is a valuable research tool for studying FLT3-driven hematological cancers in both cellular and animal models.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 387867-13-2
• MW: 562.7
• Purity: 99.92% (May vary between batches)
• Formula: C₃₁H₄₂N₆O₄
• SMILES: O(C)C1=CC=2C(=NC=NC2C=C1OCCCN3CCCCC3)N4CCN(C(NC5=CC=C(OC(C)C)C=C5)=O)CC4
• Target: FLT,Src,CSF-1R,c-Kit,PDGFR,Apoptosis
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.55 mM);Ethanol:6 mg/mL (10.66 mM);DMSO:50 mg/mL (88.86 mM)

Bioactivity

• Target IC50:
  c-Kit:0.17 μM|FLT3:0.22 μM|PDGFR:0.2 μM
• In Vivo:
  Unlike Staurosporine, Tandutinib demonstrates superior inhibition of βPDGF, FLT3, and c-Kit autophosphorylation (IC50: 0.17-0.22 μM), while exerting minimal effect on EGFR, FGFR, KDR, InsR, Src, Abl, PKC, PKA, and MAPKs. Tandutinib exhibits specificity towards inhibiting FLT3, effectively inducing apoptosis in FLT3-ITD positive Molm-14 cells (51% and 78% at 24 and 96 hours, respectively) but not in FLT3-ITD negative THP-1 cells. This compound preferentially restricts the explosive colony growth in FLT3 ITD positive AML patients without affecting the colony formation of normal progenitor cells. Moreover, Tandutinib inhibits cell growth independent of IL-3 and suppresses FLT3-ITD autophosphorylation (IC50: 10-100 nM). It also impedes the proliferation of Ba/F3 cells with FLT3-ITD mutation (IC50: 10-30 nM) and targets FLT3-ITD-positive Molm-13 and 14 cells (IC50: 10 nM), showcasing its potential therapeutic value in targeted leukemia treatments.
• In Vitro:
  In mice carrying Ba/F3 cells expressing the W51 FLT3-ITD mutation, Tandutinib (60 mg/kg, twice daily, orally) significantly extends lifespan. In a mouse bone marrow transplantation model, it also significantly reduces mortality rates. Tandutinib (180 mg/kg, twice daily) exhibits minor toxicity to normal hematopoietic function and is effective in treating FLT3 ITD-positive leukemia in mice.
• Cell Research:
  Cells are exposed to increasing concentrations of Tandutinib (0.004-30 μM). Cells are grown for 3-7 days in tissue culture, and viable cells, determined by Trypan blue dye exclusion, are counted. At daily intervals, cells are harvested, washed, and resuspended in 100 uL binding buffer containing 10 mM HEPES (pH 7.4), 140 mM NaCl, and 2.5 mM CaCl2. Annexin V-FITC (100 ng) and propidium iodide (250 ng) are added to the cell suspension followed by incubation at room temperature for 15 minutes. Flow cytometry is performed immediately after staining on a FACSort flow cytometer with excitation at 488 nm. Fluorescence of annexin V-FITC and DNA propidium iodide staining are measured at 515 nm and 585 nm, respectively.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CT 53518, CT53518, CT-53518, CSF-1R, CSF1R, Cluster of differentiation antigen 135, CD135, CD117, c-Kit, cKit, Acute, blood-brain, Apoptosis, barrier, autophosphorylation, NSC 726292, Inhibitor, myelogenous, inhibit, MLN518, MLN-518, MLN 518, NSC726292, NSC-726292, PDGFR, Platelet-derived growth factor receptor, FLT3-ITD, FLT3, Fms like tyrosine kinase 3, MAP, leukemia, Src, SCFR, Tandutinib, PI3, PDGFRβ

Compound Identifiers

PubChem CID

3038522