| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| Other Sizes |
| Targets |
VEGFR3 110.4 nM (IC50)
VEGFR3 (Flt-4). VEGFR-3-IN-1 is a selective inhibitor of the VEGFR3 receptor tyrosine kinase with an IC50 of 110.4 nM. It is designed to block the VEGF-C/VEGFR3 signaling pathway. |
|---|---|
| ln Vitro |
With IC50 values of 2.22 and 3.50 μM, respectively, VEGFR-3-IN-1 (compound 38k) demonstrates a significantly higher antiproliferative activity on MDA-MB-231 and MDA-MB-436 cells than 10 (IC50 > 50 μM)[1]. In a dose-dependent manner, VEGFR-3-IN-1 significantly inhibits the phosphorylation of VEGFR3 and its downstream proteins[1].
VEGFR-3-IN-1 demonstrates potent in vitro activity against VEGFR3 with an IC50 of 110.4 nM. It significantly inhibits the proliferation and migration of VEGF-C-induced human dermal lymphatic endothelial cells (HDLEC). It also inhibits the migration of breast cancer cell lines MDA-MB-231 and MDA-MB-436 by inactivating the VEGFR3 signaling pathway. |
| ln Vivo |
In mice, VEGFR-3-IN-1 (50, 25 mg/kg; po) exhibits the most inhibitory efficacy, reducing the tumor volume and exhibiting a growth inhibition rate of 61.9%[1]. Treatment with 10 mg/kg of VEGFR-3-IN-1 po showed values for Cmax, AUC0-t, AUC0-∞, and t1/2 of 420 ng/mL, 9219 ng h/mL, 12304 ng h/mL, and 16 hours, respectively[1].
In a breast cancer mouse xenograft model, VEGFR-3-IN-1 (administered orally at 50 mg/kg) reduces tumor volume and displays strong inhibitory activity, with a growth inhibition rate of 61.9%. This demonstrates its antitumor activity by targeting tumor lymphangiogenesis and metastasis. |
| Enzyme Assay |
Cell-free VEGFR3 kinase assays are performed using recombinant VEGFR3 enzyme, a peptide substrate, and ATP. The compound is incubated with the enzyme, and kinase activity is measured using a luminescence-based ADP detection kit. The IC50 (110.4 nM) is calculated from a dose-response curve.
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: MDA-MB-231 and MDA-MB-436 cells Tested Concentrations: 100 nM Incubation Duration: 48 hrs (hours) Experimental Results: Exerted antimigration and antiproliferative activities through targeting VEGFR3 in MDA-MB-231 and MDA-MB-436 cells. Western Blot Analysis[1] Cell Types: HDLEC cells Tested Concentrations: 10-500 nM Incubation Duration: Experimental Results: Antilymphangiogenic activities of VEGFR-3-IN-1 by suppressing the expression of VEGFR3. Human dermal lymphatic endothelial cells (HDLEC) are seeded in a 96-well plate. After 24 hours, they are treated with VEGFR-3-IN-1 and stimulated with VEGF-C. Cell proliferation is measured using a BrdU incorporation ELISA. For migration assays, cells are seeded in a transwell chamber, and the number of cells that migrate through the membrane is counted. |
| Animal Protocol |
Animal/Disease Models: Nude mice (carrying xenografted BC)[1]
Doses: 50 mg/kg Route of Administration: Po;once Experimental Results: decreased the tumor volume, and displayed the strongest inhibitory activity in mice. Animal/Disease Models: SD (Sprague-Dawley) rats[1] Doses: 10 mg/kg Route of Administration: Po (pharmacokinetic/PK Analysis) Experimental Results: The Cmax, AUC0-t , AUC0-∞ and t1/2 were 420 ng/mL, 9219 ng h/mL, 12304 ng h/mL and 16 hrs (hours), respectively. For an in vivo breast cancer model, female BALB/c nude mice are inoculated with human breast cancer cells (e.g., MDA-MB-231). When tumors reach a certain volume, mice are treated with VEGFR-3-IN-1 by oral gavage at doses of 25 or 50 mg/kg. Tumor volumes are measured with calipers. Tumors are harvested for immunohistochemical analysis of lymphatic vessel density (LVD). |
| ADME/Pharmacokinetics |
No specific PK data are reported. The molecular weight is 333.41 (C17H16N4OS). The CAS number is 186610-88-8. For in vitro use, it is typically dissolved in DMSO to create a stock solution. In vivo formulation often involves a mixture of DMSO, PEG300, Tween-80, and saline.
|
| Toxicity/Toxicokinetics |
No specific toxicity data are reported. As a VEGFR3 inhibitor, the primary risk in a research setting is on-target-mediated effects, such as lymphedema. However, this is more relevant to long-term inhibition. The compound is for research use only and is not for human consumption.
|
| References | |
| Additional Infomation |
Other information: VEGFR-3-IN-1 is a valuable tool for dissecting the role of the VEGF-C/VEGFR-3 signaling axis in cancer metastasis, as it is the primary regulator of lymphangiogenesis. By inhibiting lymphangiogenesis, it can potentially block the spread of tumor cells to draining lymph nodes.
|
| Molecular Formula |
C29H29CLF3N7OS
|
|---|---|
| Molecular Weight |
616.100073575974
|
| Exact Mass |
615.179
|
| CAS # |
2756668-73-0
|
| PubChem CID |
156587562
|
| Appearance |
Off-white to yellow solid powder
|
| LogP |
5.8
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
42
|
| Complexity |
912
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
N1(C(NC2=CC=C(Cl)C(C(F)(F)F)=C2)=O)CCN(C2N=CN=C3SC(C4=CC=C(N5CCN(C)CC5)C=C4)=CC3=2)CC1
|
| InChi Key |
ZYZUOYYVHYGMDE-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C29H29ClF3N7OS/c1-37-8-10-38(11-9-37)21-5-2-19(3-6-21)25-17-22-26(34-18-35-27(22)42-25)39-12-14-40(15-13-39)28(41)36-20-4-7-24(30)23(16-20)29(31,32)33/h2-7,16-18H,8-15H2,1H3,(H,36,41)
|
| Chemical Name |
N-[4-chloro-3-(trifluoromethyl)phenyl]-4-[6-[4-(4-methylpiperazin-1-yl)phenyl]thieno[2,3-d]pyrimidin-4-yl]piperazine-1-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 12.5 mg/mL (20.29 mM)
|
|---|---|
| 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 | 1.6231 mL | 8.1156 mL | 16.2311 mL | |
| 5 mM | 0.3246 mL | 1.6231 mL | 3.2462 mL | |
| 10 mM | 0.1623 mL | 0.8116 mL | 1.6231 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
