SAR131675VEGFR3 inhibitor,selective and ATP-competitve CAS# 1433953-83-3 |
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Quality Control & MSDS
3D structure
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| Cas No. | 1433953-83-3 | SDF | Download SDF |
| PubChem ID | 71295845 | Appearance | Powder |
| Formula | C18H22N4O4 | M.Wt | 358.39 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 25 mg/mL (69.76 mM; Need ultrasonic) | ||
| Chemical Name | 2-amino-1-ethyl-7-[(3R)-3-hydroxy-4-methoxy-3-methylbut-1-ynyl]-N-methyl-4-oxo-1,8-naphthyridine-3-carboxamide | ||
| SMILES | CCN1C(=C(C(=O)C2=C1N=C(C=C2)C#CC(C)(COC)O)C(=O)NC)N | ||
| Standard InChIKey | PFMPOBVAYMTUOX-GOSISDBHSA-N | ||
| Standard InChI | 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)/t18-/m1/s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | SAR131675 is an inhibitor of VEGFR3 with IC50/Ki of 23 nM/12 nM, respectively. | |||||
| Targets | VEGFR3 | |||||
| IC50 | 23 nM (Ki=12 nM) | |||||
SAR131675 Dilution Calculator
SAR131675 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.7903 mL | 13.9513 mL | 27.9026 mL | 55.8051 mL | 69.7564 mL |
| 5 mM | 0.5581 mL | 2.7903 mL | 5.5805 mL | 11.161 mL | 13.9513 mL |
| 10 mM | 0.279 mL | 1.3951 mL | 2.7903 mL | 5.5805 mL | 6.9756 mL |
| 50 mM | 0.0558 mL | 0.279 mL | 0.5581 mL | 1.1161 mL | 1.3951 mL |
| 100 mM | 0.0279 mL | 0.1395 mL | 0.279 mL | 0.5581 mL | 0.6976 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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SAR131675 is a selective inhibitor of VEGFR-3 with IC50 value of 20nM [1].
SAR131675 is an ATP-competitive inhibitor. It inhibits recombinant human VEGFR-3 with IC50 value of 23nM and inhibits the kinase activity of VEGFR-3 with Ki value of 12nM. SAR131675 is found to be cell permeable and inhibits VEGFR-3 autophosphorylation in HEK cells with IC50 values ranging from 30nM to 50nM. SAR131675 shows IC50 values of >3μM and 235nM against VEGFR-1 and VEGFR-2, respectively. It also havs no inhibitory effect on a panel of 65 kinases, 107 nonkinase enzymes and receptors and on 21 ion channels. Moreover, SAR131675 inhibits lymphatic cell survival induced by VEGFC and VEGFD with IC50 values of 14nM and 17nM. On another hand, SAR131675 exerts inhibition of the migration induced by VEGFA or VEGFC with IC50 values of 100nM and <30nM in HLMVEC cells, respectively [1].
In vivo, SAR131675 abrogates lymphangiogenesis and angiogenesis induced by FGF2. It also shows antitumor activity in the mice models. Treatment with SAR131675 significantly reduces the tumor volume of 4T1 mammary carcinoma tumors [1]
References:
[1] Alam A, Blanc I, Gueguen-Dorbes G, et al. SAR131675, a Potent and Selective VEGFR-3–TK Inhibitor with Antilymphangiogenic, Antitumoral, and Antimetastatic Activities. Molecular cancer therapeutics, 2012, 11(8): 1637-1649.
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Specific Inhibition of the VEGFR-3 Tyrosine Kinase by SAR131675 Reduces Peripheral and Tumor Associated Immunosuppressive Myeloid Cells.[Pubmed:24589997]
Cancers (Basel). 2014 Feb 28;6(1):472-90.
Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) represent prominent components in cancer progression. We previously showed that inhibition of the VEGFR-3 pathway by SAR131675 leads to reduction of TAM infiltration and tumor growth. Here, we found that treatment with SAR131675 prevents the accumulation of immunosuppressive blood and splenic MDSCs which express VEGFR-3, in 4T1 tumor bearing mice. Moreover we showed that soluble factors secreted by tumor cells promote MDSCs proliferation and differentiation into M2 polarized F4/80+ macrophages. In addition, cell sorting and transcriptomic analysis of tumor infiltrating myeloid cells revealed the presence of a heterogeneous population that could be divided into 3 subpopulations: (i) immature cells with a MDSC phenotype (GR1+/CD11b+/F4/80-); (ii) "immuno-incompetent" macrophages (F4/80high/CD86neg/MHCIILow) strongly expressing M2 markers such as Legumain, CD206 and Mgl1/2 and (iii) "immuno-competent"-M1 like macrophages (F4/80Low/CD86+/MHCIIHigh). SAR131675 treatment reduced MDSCs in lymphoid organs as well as F4/80High populations in tumors. Interestingly, in the tumor SAR131675 was able to increase the immunocompetent M1 like population (F4/80low). Altogether these results demonstrate that the specific VEGFR-3 inhibitor SAR131675 exerts its anti tumoral activity by acting on different players that orchestrate immunosuppression and cancer progression in a tumoral context: MDSCs in peripheral lymphoid organs and TAMs infiltrating the tumor.
SAR131675, a potent and selective VEGFR-3-TK inhibitor with antilymphangiogenic, antitumoral, and antimetastatic activities.[Pubmed:22584122]
Mol Cancer Ther. 2012 Aug;11(8):1637-49.
SAR131675 is a potent and selective VEGFR-3 inhibitor. It inhibited VEGFR-3 tyrosine kinase activity and VEGFR-3 autophosphorylation in HEK cells with IC(50) values of 20 and 45 nmol/L, respectively. SAR131675 dose dependently inhibited the proliferation of primary human lymphatic cells, induced by the VEGFR-3 ligands VEGFC and VEGFD, with an IC(50) of about 20 nmol/L. SAR131675 was found to be highly selective for VEGFR-3 versus 107 receptors, enzymes, ion channels, and 65 kinases. However, it was moderately active on VEGFR-2 with a VEGFR-3/VEGFR-2 ratio of about 10. SAR131675 had no antiproliferative activity on a panel of 30 tumors and primary cells, further showing its high specificity and indicating that SAR131675 is not a cytotoxic or cytostatic agent. SAR131675 was very well tolerated in mice and showed a potent antitumoral effect in several orthotopic and syngenic models, including mammary 4T1 carcinoma and RIP1.Tag2 tumors. 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.
