| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
FLT3 0.22 μM (IC50) c-Kit 0.17 μM (IC50) PDGFR 0.2 μM (IC50)
Tandutinib hydrochloride targets FLT3, a receptor tyrosine kinase that is frequently mutated in acute myeloid leukemia (AML). It also inhibits c-Kit and PDGFR with similar potency. The compound is a selective FLT3 inhibitor with an IC50 of 0.22 μM. Its ability to inhibit multiple kinases contributes to its potential therapeutic effects in AML and other cancers. |
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| ln Vitro |
In Ba/F3 cells expressing various FLT3-ITD mutations, tantutinib (0-3 μM; 30 minutes) treatment suppresses FLT3-autophosphorylation and IL-3-independent cell proliferation with an IC50 of 10-100 nM[1]. FLT3-ITD-positive AML cells undergo apoptosis when treated with tantutinib (1 μM; 24-96 hours; Molm-14 and THP-1 AML cells)[1]. Tandutinib suppresses FLT3-ITD phosphorylation (IC50 of ~30 nM) in human FLT3-ITD-positive AML cell lines. Pretreating the Molm-14 cells with 100–300 nM tantutinib effectively blocks constitutively high levels of Akt phosphorylation, much as it does Erk2[1]. Tandutinib has an IC50 of 10 nM, which inhibits the FLT3-ITD-positive Molm-13 and Molm-14 cells from proliferating. as well as signaling via the PI3 kinase and MAP kinase pathways[1].
In vitro, Tandutinib hydrochloride potently inhibits FLT3 kinase activity with an IC50 of 0.22 μM. It also inhibits c-Kit and PDGFR with IC50 values of 0.17 μM and 0.20 μM, respectively. These activities have been demonstrated in biochemical assays using recombinant kinases. The compound's ability to inhibit FLT3 makes it a promising therapeutic agent for AML. |
| ln Vivo |
Tandutinib treatment results in a statistically significant improvement in survival, which is extended on average by 20 days in athymic nude mice (60 mg/kg; oral gavage; daily; for 35 days)[1].
In vivo, Tandutinib hydrochloride has been studied for its ability to treat acute myeloid leukemia. It has shown efficacy in preclinical models of AML, and its ability to cross the blood-brain barrier (BBB) suggests potential for treating central nervous system involvement in leukemia. Further studies are needed to fully characterize its in vivo activity. |
| Enzyme Assay |
The in vitro enzyme assay for Tandutinib hydrochloride typically involves measuring its inhibitory activity against FLT3, c-Kit, and PDGFR. These are kinase activity assays where the compound is incubated with the kinase, ATP, and a peptide substrate. The phosphorylation level is quantified, and IC50 values are determined. These assays confirm the compound's potency and selectivity.
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| Cell Assay |
Apoptosis Analysis[1]
Cell Types: Molm-14 and THP-1 AML cells Tested Concentrations: 1 μM Incubation Duration: 24 hrs (hours), 48 hrs (hours), 72 hrs (hours), 96 hrs (hours) Experimental Results: Induced apoptosis in FLT3 -ITD-positive AML cells. Western Blot Analysis[1] Cell Types: Ba/F3 cells Tested Concentrations: 0 μM, 0.003 μM, 0.01 μM, 0.03 μM, 0.1 μM, 1 μM and 3 μM Incubation Duration: 30 minutes Experimental Results: In Ba/F3 cells express different FLT3-ITD mutants, inhibited IL-3-independent cell growth and FLT3-ITD autophosphorylation. Cellular assays for Tandutinib hydrochloride are performed using AML cell lines that express FLT3. Cells are treated with varying concentrations of the compound, and cell viability and proliferation are assessed. The compound's ability to inhibit FLT3 signaling is confirmed by measuring downstream signaling molecules, such as phosphorylated STAT5 or ERK. |
| Animal Protocol |
Animal/Disease Models: Athymic nude mice injected with Ba/F3 cells[1]
Doses: 60 mg/kg Route of Administration: po (oral gavage); daily; for 35 days Experimental Results: Caused a statistically significant increase in survival that was extended on average by 20 days. In vivo animal protocols for Tandutinib hydrochloride involve the use of mouse xenograft models of AML. Tumor-bearing mice are treated with the compound, and tumor growth is monitored. The compound's ability to penetrate the blood-brain barrier (BBB) is assessed in these models. These studies provide preclinical evidence for its potential in treating AML. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of Tandutinib hydrochloride have been studied. It is administered orally and has shown good bioavailability. The compound has the ability to cross the blood-brain barrier (BBB), which is important for treating central nervous system involvement in leukemia. Its half-life, clearance, and volume of distribution have been characterized in preclinical studies.
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| Toxicity/Toxicokinetics |
Toxicity data for Tandutinib hydrochloride have been evaluated in preclinical studies. As a kinase inhibitor, its toxicity is primarily related to on-target and off-target effects. The compound has been shown to be generally well-tolerated in preclinical models. However, comprehensive toxicological data are not detailed in the available literature.
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| References |
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| Additional Infomation |
Tandutinib hydrochloride (MLN518 hydrochloride) is a potent and selective FLT3 inhibitor. It also inhibits c-Kit and PDGFR. The compound is used in research for acute myeloid leukemia (AML) and has the ability to cross the blood-brain barrier (BBB). It is not currently approved for clinical use and is intended for research purposes.
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| Molecular Formula |
C31H43CLN6O4
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|---|---|
| Molecular Weight |
599.163926362991
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| Exact Mass |
598.303
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| CAS # |
2438900-70-8
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| Related CAS # |
Tandutinib;387867-13-2
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| PubChem CID |
138911453
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
42
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| Complexity |
783
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O(C1C(=CC2=C(C=1)N=CN=C2N1CCN(C(NC2C=CC(=CC=2)OC(C)C)=O)CC1)OC)CCCN1CCCCC1
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| InChi Key |
FOEBHLNUCNUHHJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C31H42N6O4.ClH/c1-23(2)41-25-10-8-24(9-11-25)34-31(38)37-17-15-36(16-18-37)30-26-20-28(39-3)29(21-27(26)32-22-33-30)40-19-7-14-35-12-5-4-6-13-35;/h8-11,20-23H,4-7,12-19H2,1-3H3,(H,34,38);1H
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| Chemical Name |
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide;hydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (166.90 mM)
H2O : 100 mg/mL (166.90 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.17 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: 100 mg/mL (166.90 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6690 mL | 8.3450 mL | 16.6900 mL | |
| 5 mM | 0.3338 mL | 1.6690 mL | 3.3380 mL | |
| 10 mM | 0.1669 mL | 0.8345 mL | 1.6690 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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