SKLB610Potent VEGFR inhibitor CAS# 1125780-41-7 |
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Quality Control & MSDS
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| Cas No. | 1125780-41-7 | SDF | Download SDF |
| PubChem ID | 25230662 | Appearance | Powder |
| Formula | C21H16F3N3O3 | M.Wt | 415.4 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | >20.8mg/mL in DMSO | ||
| Chemical Name | N-methyl-4-[4-[[3-(trifluoromethyl)benzoyl]amino]phenoxy]pyridine-2-carboxamide | ||
| SMILES | CNC(=O)C1=NC=CC(=C1)OC2=CC=C(C=C2)NC(=O)C3=CC(=CC=C3)C(F)(F)F | ||
| Standard InChIKey | WACDHHMEVMSODJ-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C21H16F3N3O3/c1-25-20(29)18-12-17(9-10-26-18)30-16-7-5-15(6-8-16)27-19(28)13-3-2-4-14(11-13)21(22,23)24/h2-12H,1H3,(H,25,29)(H,27,28) | ||
| 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 | SKLB610 is a novel multi-targeted inhibitor of angiogenesis-related tyrosine kinase. | |||||
| Targets | FGFR | |||||
SKLB610 Dilution Calculator
SKLB610 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.4073 mL | 12.0366 mL | 24.0732 mL | 48.1464 mL | 60.183 mL |
| 5 mM | 0.4815 mL | 2.4073 mL | 4.8146 mL | 9.6293 mL | 12.0366 mL |
| 10 mM | 0.2407 mL | 1.2037 mL | 2.4073 mL | 4.8146 mL | 6.0183 mL |
| 50 mM | 0.0481 mL | 0.2407 mL | 0.4815 mL | 0.9629 mL | 1.2037 mL |
| 100 mM | 0.0241 mL | 0.1204 mL | 0.2407 mL | 0.4815 mL | 0.6018 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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SKLB610 is a selective inhibitor of VEGFR with IC50 value of 2.2 μM [1].
VEGFR (vascular endothelial growth factor receptor) are receptors for VEGF and plays an important role in stimulating cellular response by cooperating with VEGF. It has been reported that VEGFR abnormally expressed in a variety of cancers and its inhibitors has been regarded as a promising strategy in clinic [1, 2].
SKLB610 is a potent VEGF induced VEGF2 phosphorylation inhibitor. When tested with a panel of human cancer cell lines, SKLB610 inhibited cell proliferation with IC50 value ranges from 2.2 μM to 25.6 μM. In HUVECs, SKLB610 showed inhibition on VEGF-stimulated cell proliferation as well as VEGFR2 phosphorylation, inhibited cell capillary tube formation in a dose-dependent manner [1]. The solubility of SKLB610 in water, Ethanol, Ethyl acetate, 0.5% Tween 80 and Nanosuspension is 0.34 μg/ml, 16500 μg/ml, 380μg/ml, 23μg/ml and 103μg/ml [2, 3].
In mouse model with HCT116 subcutaneous xenograft, administration of SKLB610 (12.5 mg/kg, 25 mg/kg and 50 mg/kg) for 10 days markedly delayed tumor growth in a concentration dependent manner. Further, after 30 days treatment SKLB610significantly suppressed tumor volume as 77.1 % at the dose of 50 mg/kg [1].
References:
[1]. Cao, Z.X., et al., SKLB610: a novel potential inhibitor of vascular endothelial growth factor receptor tyrosine kinases inhibits angiogenesis and tumor growth in vivo. Cell Physiol Biochem, 2011. 27(5): p. 565-74.
[2]. Luo, X., et al., Pharmacokinetic studies of a novel multikinase inhibitor for treating cancer by HPLC-UV. J Chromatogr Sci, 2013. 51(1): p. 17-20.
[3]. Huang, Y., et al., The preparation and evaluation of water-soluble SKLB610 nanosuspensions with improved bioavailability. AAPS PharmSciTech, 2013. 14(3): p. 1236-43.
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The preparation and evaluation of water-soluble SKLB610 nanosuspensions with improved bioavailability.[Pubmed:23934433]
AAPS PharmSciTech. 2013 Sep;14(3):1236-43.
The aim of the study was to investigate the potential of nanosuspension to enhance the bioavailability of SKLB610 (Biopharmaceutical Classification System class II drug), a bioactive anticancer compound synthesized in our labs. SKLB610 nanosuspensions were prepared using wet media milling. Physicochemical characteristics of the nanosuspensions were evaluated, including particle size and distribution, dissolution, transmission electron microscopy, atomic force microscopy, thermogravimetric analysis, and X-ray powder diffractometry. The dissolution rate of SKLB610 was greatly improved in nanosuspensions, compared to crude SKLB610. Pharmacokinetic studies in rats demonstrated that the oral bioavailability of SKLB610 in nanosuspension (89.4%) was 2.6-fold higher than in coarse suspension (34.1%). Stabilizer type, milling time, and milling speed had a significant effect on particle size of the SKLB610 nanosuspensions. Nanosuspensions effectively improved the dissolution rate and bioavailability of the water-insoluble drug SKLB610 by reducing the compound particle size to the nanoscale and employing a proper formulation.
SKLB610: a novel potential inhibitor of vascular endothelial growth factor receptor tyrosine kinases inhibits angiogenesis and tumor growth in vivo.[Pubmed:21691074]
Cell Physiol Biochem. 2011;27(5):565-74.
Antagonizing angiogenesis-related receptor tyrosine kinase is a promising therapeutic strategy in oncology. In present study, we designed and synthesized a novel vascular endothelial growth factor receptor (VEGFR) inhibitor N-methyl-4-(4-(3-(trifluoromethyl) benzamido) phenoxy) picolinamide SKLB610 that potently suppresses human tumor angiogenesis. SKLB610 inhibited angiogenesis-related tyrosine kinase VEGFR2, fibroblast growth factor receptor 2 (FGFR2) and platelet-derived growth factor receptor (PDGFR) at rate of 97%, 65% and 55%, respectively, at concentration of 10muM in biochemical kinase assays. In vitro, SKLB610 showed more selective inhibition of VEGF-stimulated human umbilical vein endothelial cells (HUVECs) proliferation, and this proliferation inhibitory effect was associated with decreased phosphorylation of VEGFR2 and p42/44 mitogen-activated protein kinase (p42/44 MAPK). Antiangiogenic evaluation showed that SKLB610 inhibited the HUVECs capillary-tube formation on Matrigel in vitro and the sub-intestinal vein formation of zebrafish in vivo. Moreover, SKLB610 inhibited a panel of human cancer cells proliferation in a concentration-dependent manner and human non-small cell lung cancer cell line A549 and human colorectal cancer cell line HCT116 were most sensitive to SKLB610 treatment. In vivo, chronic intraperitoneally administration of SKLB610 at dose of 50mg/kg/d resulted in significant inhibition in the growth of established human A549 and HCT116 tumor xenografts in nude mice without exhibit toxicity. Histological analysis showed significant reductions in intratumoral microvessel density (CD31 staining) of 43-55% relative to controls depending on the specific tumor xenografts. In conclusion, the present study demonstrated that SKLB610 exhibited its antitumor activity as a multi-targeted inhibitor with more potent inhibition of VEGFR2 activity. Its potential to be a candidate of anticancer agent is worth being further investigated.
