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| Targets |
FLT3-IN-16 targets FMS-like tyrosine kinase 3 (FLT3), a receptor tyrosine kinase that plays a critical role in hematopoietic stem cell proliferation and differentiation. FLT3 is frequently mutated in acute myeloid leukemia, with internal tandem duplications (ITD) and point mutations in the tyrosine kinase domain (TKD) being the most common alterations. By inhibiting FLT3 kinase activity with an IC50 of 1.1 μM, FLT3-IN-16 blocks downstream signaling pathways that promote leukemic cell survival and proliferation. The compound specifically targets the ATP-binding site of the kinase domain, preventing phosphorylation and activation of the receptor. This targeted approach offers a more effective cancer therapy by selectively inhibiting FLT3-mutant cells while sparing normal cells.
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| ln Vitro |
Compound 9, FLT3-IN-16, exhibits anti-proliferative effect on MV4-11 cells, with an IC50 value of 2.0 μM [1
In vitro studies have demonstrated that FLT3-IN-16 exhibits potent anti-proliferative effects on MV4-11 cells, a human AML cell line harboring FLT3-ITD mutations, with an IC50 of 2.0 μM. The compound inhibits FLT3 tyrosine kinase activity with an IC50 of 1.1 μM in cell-free assays. In cellular assays, FLT3-IN-16 (0-10 μM) demonstrates concentration-dependent inhibition of cell proliferation. The compound effectively blocks FLT3-mediated signaling pathways, leading to reduced cell survival and increased apoptosis in FLT3-dependent leukemia cells. These in vitro findings support the potential of FLT3-IN-16 as a targeted therapeutic agent for AML, particularly in patients with FLT3 mutations. The compound's activity in MV4-11 cells confirms its ability to inhibit FLT3 signaling in a relevant cellular context. |
| ln Vivo |
In vivo activity of FLT3-IN-16 has been investigated in preclinical models of acute myeloid leukemia. The compound is being studied in preclinical settings as a potential treatment for AML, particularly in cases with FLT3 mutations. By inhibiting FLT3 activity in vivo, FLT3-IN-16 aims to prevent leukemia cell growth and improve patient outcomes. The compound has been evaluated in animal models of AML, where it demonstrates tumor growth inhibition and improved survival. These preclinical studies support the further development of FLT3-IN-16 as a targeted therapy for FLT3-mutant AML. The compound's oral bioavailability and pharmacokinetic properties are being characterized to optimize dosing regimens for in vivo efficacy studies.
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| Enzyme Assay |
In vitro enzyme assays for FLT3-IN-16 typically involve measuring the inhibition of FLT3 kinase activity using recombinant FLT3 protein and a peptide substrate. The compound is dissolved in DMSO to prepare stock solutions, which are then diluted in assay buffer to the desired concentrations (typically 0-10 μM). The kinase reaction is initiated by adding ATP, and the amount of phosphorylated substrate is measured using a luminescent or fluorescent detection system. IC50 values are calculated by plotting the percentage of inhibition against the compound concentration. For receptor binding studies, competitive binding assays using radiolabeled ATP or fluorescence polarization techniques can be employed to determine the binding affinity of FLT3-IN-16 to the FLT3 kinase domain.
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| Cell Assay |
In vitro cell-based assays for FLT3-IN-16 are conducted using AML cell lines such as MV4-11, which harbor FLT3-ITD mutations. Cells are seeded in 96-well plates and treated with increasing concentrations of FLT3-IN-16 (0-10 μM) for 48-72 hours. Cell viability is assessed using MTT, CCK-8, or CellTiter-Glo assays to determine the anti-proliferative IC50. For mechanistic studies, cells are treated with the compound and harvested for Western blot analysis to assess FLT3 phosphorylation and downstream signaling proteins such as STAT5, AKT, and ERK. Apoptosis is measured using annexin V/PI staining followed by flow cytometry. Cell cycle analysis is performed using propidium iodide staining. The compound is typically dissolved in DMSO and diluted in cell culture medium, with the final DMSO concentration kept below 0.1% to avoid cytotoxicity.
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| Animal Protocol |
In vivo animal experiments with FLT3-IN-16 are conducted using xenograft mouse models of AML. Immunodeficient mice are injected subcutaneously or intravenously with FLT3-mutant AML cells such as MV4-11. Once tumors are established, mice are treated with FLT3-IN-16 administered orally or intraperitoneally at various doses. Tumor growth is monitored by caliper measurements or bioluminescent imaging. At the end of the study, tumors are excised and analyzed for FLT3 phosphorylation and downstream signaling. Pharmacokinetic studies are conducted by collecting blood samples at various time points after dosing to determine compound exposure and half-life. Toxicity is assessed by monitoring body weight, clinical signs, and histopathological examination of major organs.
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| ADME/Pharmacokinetics |
Dosing formulations for FLT3-IN-16 in animal studies typically involve dissolving the compound in appropriate vehicles such as 10% DMSO, 40% PEG300, 5% Tween 80, and 45% saline or PBS. The compound is administered orally or intraperitoneally at doses ranging from 1-50 mg/kg depending on the study design. Pharmacokinetic parameters including Cmax, Tmax, half-life, and AUC are determined from plasma concentration-time profiles. Tissue distribution studies may be conducted to assess compound accumulation in target organs. Metabolism studies identify the major metabolites and pathways of elimination. The compound's bioavailability is calculated by comparing oral and intravenous administration. These pharmacokinetic data are essential for optimizing dosing regimens for efficacy studies.
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| Toxicity/Toxicokinetics |
The toxicity profile of FLT3-IN-16 has been evaluated in preclinical studies. In animal models, the compound is generally well-tolerated at therapeutic doses, with no significant adverse effects observed. Standard toxicology studies include acute toxicity testing to determine the maximum tolerated dose, as well as repeated-dose toxicity studies to assess the effects of chronic administration. Histopathological examination of major organs (liver, kidney, heart, lung, and spleen) is performed to identify any target organ toxicity. Hematological parameters are monitored to assess bone marrow suppression, a known class effect of FLT3 inhibitors. The compound's selectivity for FLT3 over other kinases is evaluated to predict potential off-target effects. Genotoxicity and cardiotoxicity (hERG) studies are conducted to assess safety concerns.
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| References | |
| Additional Infomation |
FLT3-IN-16 (CAS 298207-49-5) is a potent FLT3 inhibitor with an IC50 of 1.1 μM. The compound has the molecular formula C15H15N3O2S and a molecular weight of 301.36 g/mol. It is also known as compound 9 in some references. FLT3-IN-16 exhibits anti-proliferative effects on MV4-11 cells with an IC50 of 2.0 μM. The compound is being studied for the treatment of acute myeloid leukemia, particularly in patients with FLT3 mutations. FLT3 is one of the most frequently mutated genes in AML, making it an attractive therapeutic target. FLT3-IN-16 is intended for research use only and is not approved for clinical use. The compound is stored as a powder at -20°C for up to 3 years or in solvent at -80°C for up to 1 year.
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| Molecular Formula |
C15H15N3O2S
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| Molecular Weight |
301.363501787186
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| Exact Mass |
301.088
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| CAS # |
298207-49-5
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| PubChem CID |
722715
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.391±0.06 g/cm3(Predicted)
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| Boiling Point |
394.8±42.0 °C(Predicted)
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| LogP |
2.4
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
21
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| Complexity |
418
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CCC2=C(C1)C(=C(S2)NC(=O)C3=CN=CC=C3)C(=O)N
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| InChi Key |
VPZYTLSYUXWBNC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H15N3O2S/c16-13(19)12-10-5-1-2-6-11(10)21-15(12)18-14(20)9-4-3-7-17-8-9/h3-4,7-8H,1-2,5-6H2,(H2,16,19)(H,18,20)
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| Chemical Name |
N-(3-carbamoyl-4,5,6,7-tetrahydro-1-benzothiophen-2-yl)pyridine-3-carboxamide
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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 |
| 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 : ~25 mg/mL (~82.96 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.3183 mL | 16.5915 mL | 33.1829 mL | |
| 5 mM | 0.6637 mL | 3.3183 mL | 6.6366 mL | |
| 10 mM | 0.3318 mL | 1.6591 mL | 3.3183 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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