| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
VEGFR2 (IC50 = 50 nM); VEGFR1 (IC50 = 2 nM); PDGFRβ (IC50 = 4 nM); KIT (IC50 = 15 nM)
SU14813 maleate targets multiple receptor tyrosine kinases, including VEGFR1, VEGFR2, PDGFRbeta, KIT, FLT3, and CSF1R/FMS. It exhibits IC50 values of 2 nM for VEGFR1, 50 nM for VEGFR2, 4 nM for PDGFRbeta, and 15 nM for KIT. In cellular assays, SU14813 inhibits VEGFR-2, PDGFR-beta, and KIT phosphorylation in porcine aorta endothelial cells with cellular IC50 values of 5.2, 9.9, and 11.2 nM, respectively. The compound is selective for these kinases over FGFR1, EGFR, Src, and c-Met. Its mechanism involves inhibition of key regulators of tumor angiogenesis, growth, and survival. |
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| ln Vitro |
SU14813 suppresses the growth, migration, and survival of endothelial cells and/or tumor cells that express these targets both in ligand-dependent and ligand-independent ways. When it comes to transfected NIH 3T3 cells, FLT3-internal tandem duplication (FLT3-ITD; MV4;11 cells), KIT (Mo7e cells), PDGFR-β (transfected NIH 3T3 cells), and FMS/CSF1R (transfected NIH 3T3 cells), SU14813 inhibits their cellular ligand-dependent phosphorylation. In pig aorta endothelial cells overexpressing VEGFR-2, PDGFR-β, and KIT phosphorylation, SU14813 inhibits these processes with cellular IC50 values of 5.2, 9.9, and 11.2 nM, respectively. U-118MG's growth is inhibited by SU14813, with an IC50 of 50–100 nM[1].
In vitro studies have demonstrated that SU14813 maleate is a potent multi-targeted receptor tyrosine kinase inhibitor. It inhibits the growth of U-118MG glioblastoma cells with an IC50 of 50 to 100 nM. The compound inhibits VEGFR-2, PDGFR-beta, and KIT phosphorylation in porcine aorta endothelial cells overexpressing these targets, with cellular IC50 values of 5.2, 9.9, and 11.2 nM, respectively. Its potency against VEGFR2 (IC50 = 50 nM) is superior to SU6668 (2.43 microM) and comparable to or more potent than sunitinib (IC50 = 9-80 nM), depending on the specific assay format. |
| ln Vivo |
SU14813 exhibits dose- and time-dependent inhibition of VEGFR-2, PDGFR-β, and FLT3 phosphorylation in xenograft tumors. An estimated 100–200 ng/mL of plasma is needed for in vivo target inhibition. When used as monotherapy, SU14813 demonstrates extensive and strong antitumor activity, causing a variety of established xenografts made from rat or human tumor cell lines to regress, grow to a stop, or grow much less. When treatment is combined with docetaxel, compared to when either drug is administered alone, both the inhibition of primary tumor growth and the survival of the tumor-bearing mice are significantly increased[1].
In vivo studies have shown that SU14813 maleate inhibits VEGFR-2, PDGFR-beta, and FLT3 phosphorylation in xenograft tumors in a dose- and time-dependent fashion. The compound is orally bioavailable and demonstrates antitumor activity in various preclinical cancer models. As a multi-targeted TKI, it exerts anti-angiogenic effects by inhibiting VEGF-mediated signaling. The compound's in vivo efficacy has been evaluated in xenograft models of human cancer, where it inhibits tumor growth and angiogenesis. Detailed dose-response studies have been conducted to establish the optimal dosing regimens for efficacy studies. |
| Enzyme Assay |
The in vitro enzyme assay for SU14813 maleate involves kinase activity measurements using purified recombinant kinase domains. The compound is incubated with the kinase of interest (VEGFR1, VEGFR2, PDGFRbeta, KIT, FLT3, etc.) in the presence of ATP and a suitable peptide substrate. Kinase activity is measured using methods such as radiometric assays, fluorescence polarization, or ELISA. IC50 values are determined from dose-response curves. Selectivity profiling is performed using panels of kinases including FGFR1, EGFR, Src, and c-Met. Data analysis using nonlinear regression models yields inhibition constants and confirms target engagement.
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| Cell Assay |
The impact of SU14813 on the survival of endothelial cells is assessed. Human umbilical vein endothelial cells in passages 4 through 5 are cultured to subconfluency in EGM2 medium with 10% FBS, endothelial cell growth supplement, and 10 μg/mL sodium heparin. Ten thousand cells per well of F12K medium containing 10% FBS are seeded in 96-well plates. After starving the cells in F12K+1% FBS for eighteen hours the following day, SU14813 is added to the cells at different concentrations. After forty-five minutes, the assay is reconstituted with 20 ng/mL of growth factor (VEGF or basic fibroblast growth factor, bFGF). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay is used to calculate cell counts three days later[1].
In vitro cellular assays for SU14813 maleate are conducted using cell lines such as U-118MG glioblastoma cells or porcine aorta endothelial cells overexpressing VEGFR-2, PDGFR-beta, or KIT. Cells are treated with varying concentrations of SU14813, and receptor phosphorylation is assessed by Western blotting or ELISA using phospho-specific antibodies. Cell proliferation is measured using MTT or BrdU incorporation assays. The cellular IC50 values for inhibition of VEGFR-2, PDGFR-beta, and KIT phosphorylation are 5.2, 9.9, and 11.2 nM, respectively. Cell viability and specificity are confirmed using appropriate controls and selective inhibitors. |
| Animal Protocol |
Mouse: In a murine LLC model resistant to docetaxel, SU14813's effectiveness and synergism with the microtubule inhibitor docetaxel are assessed. On day five following tumor implantation, SU14813 is given p.o. twice daily (BID) at doses of 10, 40, 80, or 120 mg/kg. Commencing on day 5 following tumor implantation, docetaxel 40 mg/kg (the maximum tolerated dose in mice) is injected intravenously three times a week[1].
In vivo animal studies for SU14813 maleate are performed in xenograft mouse models of human cancer. Tumor-bearing mice are administered SU14813 via oral gavage at various doses. Tumor growth is monitored by caliper measurements, and tumor tissues are collected at endpoint for histopathological analysis and biomarker assessment. Receptor phosphorylation (VEGFR-2, PDGFR-beta, FLT3) in tumor tissues is measured to confirm target engagement. Angiogenesis is assessed by measuring microvessel density using immunohistochemistry. Standard xenograft study designs with appropriate control groups are employed. Blood samples are collected for pharmacokinetic analysis. |
| ADME/Pharmacokinetics |
Pharmacokinetic data for SU14813 maleate indicate that the compound is orally bioavailable. It is a small molecule TKI with a molecular weight consistent with oral absorption. The compound's pharmacokinetic properties have been evaluated in preclinical species to support in vivo efficacy studies. Specific parameters such as half-life, Cmax, AUC, and bioavailability are not extensively reported in the available literature. The compound is formulated for oral administration in animal studies. Its metabolic stability and clearance would be consistent with other multi-targeted TKIs of similar chemical class.
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| Toxicity/Toxicokinetics |
Toxicology data for SU14813 maleate are not extensively reported in the available literature. As a multi-targeted tyrosine kinase inhibitor, the compound's safety profile would include potential effects on normal tissues expressing VEGFR, PDGFR, and KIT. Common toxicities associated with TKIs include hypertension, fatigue, and gastrointestinal effects. However, specific toxicity data, including LD50 values, organ toxicity profiles, and genotoxicity assessments, are not readily available. Standard preclinical safety evaluations would be required for therapeutic development.
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| References | |
| Additional Infomation |
SU14813 maleate is an orally bioavailable, multi-targeted receptor tyrosine kinase inhibitor with IC50s of 50, 2, 4, and 15 nM for VEGFR2, VEGFR1, PDGFRbeta, and KIT, respectively. It targets VEGFR, PDGFR, KIT, and FLT-3 and exhibits potent anti-angiogenesis and antitumor activity. The compound inhibits the growth of U-118MG cells with an IC50 of 50-100 nM and shows cellular IC50 values of 5.2, 9.9, and 11.2 nM for VEGFR-2, PDGFR-beta, and KIT phosphorylation. SU14813 maleate is a research compound and is not approved for therapeutic use.
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| Molecular Formula |
C27H31FN4O8
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|---|---|
| Molecular Weight |
558.55544
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| Exact Mass |
558.213
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| CAS # |
849643-15-8
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| Related CAS # |
SU14813;627908-92-3
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| PubChem CID |
11353475
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| Appearance |
Yellow to orange solid
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| LogP |
1.995
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
40
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| Complexity |
848
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C(/C(=O)O)=C/C(=O)O.C(/C1NC(C)=C(C(=O)NC[C@H](O)CN2CCOCC2)C=1C)=C1/C(=O)NC2C=CC(=CC/1=2)F
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| InChi Key |
PQPBIMIFGPFTNF-FYOMJGPWSA-N
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| InChi Code |
InChI=1S/C23H27FN4O4.C4H4O4/c1-13-20(10-18-17-9-15(24)3-4-19(17)27-22(18)30)26-14(2)21(13)23(31)25-11-16(29)12-28-5-7-32-8-6-28;5-3(6)1-2-4(7)8/h3-4,9-10,16,26,29H,5-8,11-12H2,1-2H3,(H,25,31)(H,27,30);1-2H,(H,5,6)(H,7,8)/b18-10-;2-1-/t16-;/m0./s1
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| Chemical Name |
(Z)-but-2-enedioic acid;5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide
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| Synonyms |
SU14813 maleate
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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: ~66.7 mg/mL (~119.4 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.48 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 25.0 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: ≥ 2.5 mg/mL (4.48 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7903 mL | 8.9516 mL | 17.9032 mL | |
| 5 mM | 0.3581 mL | 1.7903 mL | 3.5806 mL | |
| 10 mM | 0.1790 mL | 0.8952 mL | 1.7903 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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