| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
Tie2
TIE-2 and VEGFR-2 (kinase domains). The compound is an intermediate used in the synthesis of inhibitors targeting these two receptor tyrosine kinases, which are key regulators of angiogenesis. |
|---|---|
| ln Vitro |
TIE-2 is a new angiogenic factor, and Angiopoieten 1 is a ligand for the endotheiium-specific receptor tyrosine kinase[1]. It is anticipated that TIE-2 inhibition will interfere with the remodeling and maturation of newly formed vasculature, which is started by angiogenesis and thus interferes with the angiogenic process. Tyrosine residue phosphorylation would be prevented by inhibition at the VEGFR-2 kinase domain binding site, which would also interfere with the start of angiogenesis.
The specific IC50 values of TIE-2/VEGFR-2 kinase-IN-1 as an inhibitor are not reported, as it is primarily an intermediate. Related compounds (e.g., kinase-IN-2) are dual inhibitors with pIC50 values of 8.61 for VEGFR2 and 8.56 for Tie-2. Its activity is assumed to be similar, as it is a core scaffold. |
| ln Vivo |
Specific in vivo activity data are not reported for this compound. The target class, however, is validated for the study of diseases associated with inappropriate angiogenesis. Inhibiting TIE-2 disrupts the remodeling and maturation of new vasculature, while VEGFR-2 inhibition blocks the initiation of angiogenesis.
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| Enzyme Assay |
Cell-free kinase assays are performed using recombinant TIE-2 and VEGFR-2 enzymes. The compound (or an inhibitor synthesized from it) is incubated with the enzyme, a peptide substrate, and ATP. The phosphorylation level is measured using a luminescent ADP detection kit. IC50 values are determined from dose-response curves.
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| Cell Assay |
Cellular assays are performed with primary human umbilical vein endothelial cells (HUVECs). Cells are stimulated with VEGF-A to induce proliferation and tube formation in the presence or absence of the test compound. Inhibitory effects on angiogenesis are quantified by measuring cell proliferation (BrdU) or tube length.
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| Animal Protocol |
For in vivo angiogenesis studies, the murine Matrigel plug assay or the corneal micropocket assay is used. Matrigel mixed with VEGF is injected subcutaneously into mice. The test compound is administered orally. After the study period, the Matrigel plug is removed, and hemoglobin content is measured to quantify neovascularization.
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data are reported. The molecular weight is 241.25 (C13H11N3O2), and the CAS number is 453590-24-4. For in vitro experiments, the compound is dissolved in DMSO to prepare stock solutions. For in vivo studies, it is formulated using a 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline mixture.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for this intermediate compound. As a scaffold for angiogenesis inhibitors, toxicity profiles would be related to the final drug candidate and target class effects, such as hypertension, fatigue, and gastrointestinal perforation. This compound is strictly for research use.
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| References | |
| Additional Infomation |
Other information: TIE-2/VEGFR-2 kinase-IN-1 is derived from patent WO2003022852. It is a valuable chemical building block for designing novel anti-angiogenic agents for research into diseases such as cancer and diabetic retinopathy. It is not an approved drug.
|
| Molecular Formula |
C13H11N3O2
|
|---|---|
| Molecular Weight |
241.25
|
| Exact Mass |
241.085
|
| CAS # |
453590-24-4
|
| PubChem CID |
5329802
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| Appearance |
Yellow to brown solid powder
|
| LogP |
3.061
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
18
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| Complexity |
281
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC=C(C=C1)C2=CC3=C(N=CN=C3O2)N
|
| InChi Key |
DIJLFIHLUYAZCI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C13H11N3O2/c1-17-9-4-2-8(3-5-9)11-6-10-12(14)15-7-16-13(10)18-11/h2-7H,1H3,(H2,14,15,16)
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| Chemical Name |
6-(4-methoxyphenyl)furo[2,3-d]pyrimidin-4-amine
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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: 5 mg/mL (20.73 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 4 mg/mL (16.58 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 40.0 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: ≥ 4 mg/mL (16.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 40.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1451 mL | 20.7254 mL | 41.4508 mL | |
| 5 mM | 0.8290 mL | 4.1451 mL | 8.2902 mL | |
| 10 mM | 0.4145 mL | 2.0725 mL | 4.1451 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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