Tandutinib

SKU: orb1225137

Description

A potent inhibitor of FLT3, Kit and PDGFR with IC50 of 0.22, 0.17 and 0.2 uM, respectively; displays 15-20-fold less potent activity against CSF-1R; inhibits IL-3-independent cell growth and FLT3-ITD autophosphorylation with IC50 of 10-100 nM, induces apoptosis and inhibits FLT3-ITD phosphorylation, cellular proliferation and signaling through MAPK and PI3K pathways; exhibits ativity in murine models of FLT3-ITD-mediated disease.Brain Cancer Phase 2 Discontinued(In Vitro):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.Tandutinib (1 μM; 24-96 hours; Molm-14 and THP-1 AML cells) treatment induces apoptosis in FLT3-ITD-positive AML cells.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.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.(In Vivo):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.

Key Properties

• CAS Number: 387867-13-2
• MW: 562.703
• Purity: >98% (HPLC)
• Formula: C₃₁H₄₂N₆O₄
• SMILES: O=C(N1CCN(C2=C3C=C(OC)C(OCCCN4CCCCC4)=CC3=NC=N2)CC1)NC5=CC=C(OC(C)C)C=C5
• Target: FLT3
• Solubility: DMSO: ≥ 36 mg/mL

Bioactivity

• In Vivo:
  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. Animal model: Athymic nude mice injected with Ba/F3 cells. Dosage: 60 mg/kg. Administration: Oral gavage; daily; for 35 days. Result: Caused a statistically significant increase in survival that was extended on average by 20 days.
• In Vitro:
  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. Tandutinib (1 μM; 24-96 hours; Molm-14 and THP-1 AML cells) treatment induces apoptosis in FLT3-ITD-positive AML cells. 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. 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. Apoptosis Analysis Cell line: Molm-14 and THP-1 AML cells. Concentration: 1 μM. Incubation time: 24 hours, 48 hours, 72 hours, 96 hours. Result: Induced apoptosis in FLT3-ITD-positive AML cells. Western blot analysis. Cell line: Ba/F3 cells. Concentration: 0 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 1 μM and 3 μM Incubation time: 30 minutes. Result: In Ba/F3 cells expressing different FLT3-ITD mutants, inhibited IL-3-independent cell growth and FLT3-ITD autophosphorylation.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

MLN-518 | MLN518 | CT53518 | MLN0518 | MLN-0518 | CT-53518

Quick Database Links

Gene Symbol

FLT3