| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| 500mg | |||
| 1g | |||
| Other Sizes |
| Targets |
VEGFR3
(Rac)-SAR131675 targets VEGFR3, a receptor tyrosine kinase that is activated by VEGF-C and VEGF-D. By inhibiting VEGFR3, it blocks the downstream signaling pathways that promote lymphatic endothelial cell proliferation, migration, and survival, thereby inhibiting lymphangiogenesis. This makes it a valuable tool for studying the role of VEGFR3 in tumor metastasis and other lymphatic disorders. |
|---|---|
| ln Vitro |
With an IC50 of 23 nM, SAR131675 is a strong and selective inhibitor of VEGFR3[1][2].
In vitro, SAR131675 inhibits VEGFR-3 tyrosine kinase activity with an IC50 of 20 nmol/L. It also inhibits VEGFR-3 autophosphorylation in HEK cells with an IC50 of 45 nmol/L. These studies confirm its potent and selective activity against VEGFR3. The racemate is expected to have similar activity. |
| ln Vivo |
Interestingly, it significantly reduced lymph node invasion and lung metastasis, showing its antilymphangiogenic activity in vivo. Moreover, treatment of mice before resection of 4T1 primary tumors was sufficient to prevent metastasis. Tumor-associated macrophages (TAM) play an important role in tumor growth and metastasis. The expression of VEGFR-3 on TAMs has been recently described. F4/80 immunostaining clearly showed that SAR131675 significantly reduced TAM infiltration and aggregation in 4T1 tumors. Taken together, SAR131675 is the first highly specific VEGFR-3-TK inhibitor described to date, displaying significant antitumoral and antimetastatic activities in vivo through inhibition of lymphangiogenesis and TAM invasion[2].
In vivo, SAR131675 has demonstrated antitumoral and antimetastatic activities. By inhibiting VEGFR3-mediated lymphangiogenesis, it reduces tumor metastasis to lymph nodes. These in vivo studies provide evidence for its therapeutic potential in cancer. |
| Enzyme Assay |
The contribution of many neuronal kinases to the adaptation of nerve cells to ischemic damage and their effect on functional neural network activity has not yet been studied. The aim of this work is to study the role of the four kinases belonging to different metabolic cascades (SRC, Ikkb, eEF2K, and FLT4) in the adaptive potential of the neuron-glial network for modeling the key factors of ischemic damage. We carried out a comprehensive study on the effects of kinases blockade on the viability and network functional calcium activity of nerve cells under ischemic factor modeling in vitro. Ischemic factor modelling was performed on day 14 of culturing primary hippocampal cells obtained from mouse embryos (E18). The most significant neuroprotective effect was shown in the blockade of FLT4 kinase in the simulation of hypoxia. The studies performed revealed the role of FLT4 in the development of functional dysfunction in cerebrovascular accidents and created new opportunities for the study of this enzyme and its blockers in the formation of new therapeutic strategies[1].
Cell-free assays for (Rac)-SAR131675 typically involve measuring its inhibitory activity against VEGFR3 kinase using a biochemical kinase assay. The IC50 value of 23 nM is determined by measuring the phosphorylation of a substrate in the presence of varying concentrations of the compound. These assays are used to characterize the compound's potency and selectivity against VEGFR3. |
| Cell Assay |
In vitro cellular assays are conducted to evaluate the functional activity of (Rac)-SAR131675. HEK cells expressing VEGFR3 are treated with the compound, and VEGFR-3 autophosphorylation is measured to assess the inhibition of VEGF-C-induced signaling. Lymphatic endothelial cell proliferation and migration assays are used to evaluate the compound's anti-lymphangiogenic activity. These assays confirm that (Rac)-SAR131675 effectively blocks VEGFR3-mediated cellular responses.
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| Animal Protocol |
In vivo animal experiments typically involve xenograft models of cancer or models of lymphangiogenesis. Animals are administered the compound via oral gavage or injection. Tumor growth, lymph node metastasis, or lymphangiogenesis is monitored over time to assess efficacy. These studies provide evidence for the compound's anti-tumor and anti-metastatic activity.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of (Rac)-SAR131675 are typical of a small molecule kinase inhibitor. Its molecular weight is 358.39, and its chemical formula is C18H22N4O4. The compound is designed to have favorable drug-like properties, including good permeability and metabolic stability. Pharmacokinetic studies in animal models involve measuring plasma concentrations of the compound over time to determine its half-life, clearance, and volume of distribution.
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| Toxicity/Toxicokinetics |
The toxicity profile of (Rac)-SAR131675 is not extensively documented, but it is likely to be similar to other VEGFR inhibitors. Common adverse effects may include hypertension, fatigue, and proteinuria, which are associated with the inhibition of VEGF signaling. In preclinical studies, the compound has been shown to be well-tolerated at therapeutic doses, with a safety profile that supports its use in research.
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| References | |
| Additional Infomation |
(Rac)-SAR131675 is a research compound used to study the role of VEGFR3 in lymphangiogenesis and tumor metastasis. It is the racemate of SAR131675, a potent and selective VEGFR3 inhibitor. The compound is not approved for therapeutic use and is intended for research purposes only.
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| Molecular Formula |
C18H22N4O4
|
|---|---|
| Molecular Weight |
358.39
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| Exact Mass |
358.164
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| Elemental Analysis |
C, 60.32; H, 6.19; N, 15.63; O, 17.86
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| CAS # |
1092539-44-0
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| Related CAS # |
SAR131675;1433953-83-3
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| PubChem CID |
67081200
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
592.2±50.0 °C at 760 mmHg
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| Flash Point |
312.0±30.1 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.626
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| LogP |
-0.61
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
6
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| Heavy Atom Count |
26
|
| Complexity |
677
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
CCN1C(=C(C(=O)C2=C1N=C(C=C2)C#CC(C)(COC)O)C(=O)NC)N
|
| InChi Key |
PFMPOBVAYMTUOX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C18H22N4O4/c1-5-22-15(19)13(17(24)20-3)14(23)12-7-6-11(21-16(12)22)8-9-18(2,25)10-26-4/h6-7,25H,5,10,19H2,1-4H3,(H,20,24)
|
| Chemical Name |
2-amino-1-ethyl-7-(3-hydroxy-4-methoxy-3-methylbut-1-yn-1-yl)-N-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-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)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 2.7903 mL | 13.9513 mL | 27.9026 mL | |
| 5 mM | 0.5581 mL | 2.7903 mL | 5.5805 mL | |
| 10 mM | 0.2790 mL | 1.3951 mL | 2.7903 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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