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Purity: ≥98%
Semaxanib (also known as SU5416) is a novel, potent and selective VEGFR (Flk-1/KDR) inhibitor with potential anticancer activity. It has an IC50 of 1.23 μM for inhibiting VEGFR and is 20 times more selective for VEGFR than PDGFRβ. Its activity against FGFR, InsR, and EGFR is negligible or absent. Semaxanib reversibly prevents ATP from binding to the VEGFR2 tyrosine kinase domain, which may prevent migration and proliferation of endothelial cells stimulated by VEGF and lessen the tumor microvasculature. Additionally, it prevents the phosphorylation of c-kit, a tyrosine kinase that is often expressed in acute myelogenous leukemia cells, which is a stem cell factor receptor.
| Targets |
Flk-1 (IC50 = 1.23 μM)
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| ln Vitro |
Semaxanib, with an IC50 of 1.04 μM, prevents Flk-1-overexpressing NIH 3T3 cells from phosphorylating the Flk-1 receptor in a VEGF-dependent manner. With an IC50 of 20.3 μM, semaxanib prevents PDGF-dependent autophosphorylation in NIH 3T3 cells. With an IC50 of 0.04 and 50 μM, respectively, semaxanib inhibits VEGF- and FGF-driven mitogenesis in a dose-dependent manner. The in vitro growth of C6 glioma, Calu 6 lung carcinoma, A375 melanoma, A431 epidermoid carcinoma, and SF767T glioma cells (all with IC50s > 20 μM) is unaffected by semaxanib treatment.[1]
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| ln Vivo |
Semaxanib dose-related suppresses the in vivo growth of the A375 tumor. Daily intraperitoneal administration of SU5416 in DMSO at Semaxanib results in a >85% inhibition of subcutaneous tumor growth with no detectable toxicity. Semaxanib exhibits a wide range of antitumor properties. With an average death rate of 2.5%, SU5416 significantly inhibits the subcutaneous growth of 8 out of 10 tumor lines tested (A431, Calu-6, C6, LNCAP, EPH4-VEGF, 3T3HER2, 488G2M2, and SF763T cells).[1] The tumor microvasculature's total and functional vascular densities are significantly reduced by semaxanib (25 mg/kg/day), which exhibits strong antiangiogenic activity.[2]
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| Enzyme Assay |
Polystyrene ELISA plates precoated with a Flk-1-specific monoclonal antibody are then filled with soluble membranes from 3T3 Flk-1 cells. Serial dilutions of SU5416 are added to the immunolocalized receptor following an overnight incubation at 4 °C with lysate. The ELISA plate wells containing serially diluted solutions of SU5416 are filled with varying concentrations of ATP in order to cause autophosphorylation of the receptor. After 60 minutes at room temperature, EDTA is used to halt the autophosphorylation process. The immunolocalized receptor is incubated with a biotinylated monoclonal antibody that is directed against phosphotyrosine to measure the amount of phosphotyrosine on the Flk-1 receptors in each individual well. Homo sapiens conjugated with avidin is added to the wells following the extraction of the unbound anti-phosphotyrosine antibody. Three, three, five, nine tetramethyl benzidine dihydrochloride in stabilized form is added to each well along with H2O2. H2SO4 is used to halt the reaction after 30 minutes of allowing the assay's color readout to progress.
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| Cell Assay |
HUVECs are cultivated at 37 °C for 24 hours to quiesce the cells after plating them in 96-well flat-bottomed plates (1×104 cells/100 μL/well) in F-12K media containing 0.5% heat-inactivated FBS. After adding serial dilutions of the compounds made in the medium containing 1% DMSO for two hours, the media are then supplemented with mitogenic concentrations of acidic fibroblast growth factor (0.5–5 ng/mL) or VEGF (5 ng/mL or 20 ng/mL). In the assay, the final DMSO concentration is 0.25%. After a full day, the cell monolayers are incubated for an additional 24 hours with the addition of either BrdUrd or [3H]thymidine (1 μCi/well). One can use a liquid scintillation counter or a BrdUrd ELISA to quantify the uptake of [3H]thymidine or BrdUrd into cells, respectively.
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| Animal Protocol |
Mice: At 12 weeks of age, female BALB/c nu/nu mice weighing 20–22 g are utilized. In this surgical procedure, aseptic technique is applied. The abdominal wall just above the colon has a tiny 1 cm midline incision made in it. Applying a 27-gauge needle beneath the colon's serosa allows for the implantation of C6 cells (0.5×106 cells/animal). All of the exposed intestine is reinserted into the abdominal cavity following implantation. Using a 6.0 surgical suture and wound clips, the peritoneum and skin are sealed. Seven days following surgery, the wound clips are extracted. Starting one day after implantation, the animals receive a 50 μL intraperitoneal bolus injection of either DMSO or semaxinib (SU5416) once a day. The animals are put to sleep 13–16 days after implantation, and the amount of local tumor growth on the colon is measured using venier calipers or by weighing the tumors. The formula for calculating tumor volumes is length × width × height.
Rats: Five groups of sixty male Sprague Dawley rats (n = 60, 6–8 weeks) are randomly assigned to: control (Con), pneumonectomy (PNx), semaxinib (SU), semaxinib+hypoxia (SuHx), and semaxinib+PNx (SuPNx). It uses the SuHx protocol. In short, animals receive an injection of 25 mg/kg of semaxinib dissolved in carboxymethylcellulose (CMC) and are then exposed to 10% hypoxia for four weeks before being returned to normoxia. Animals from PNx had a left pneumonectomy. A 25 mg/kg injection of semaxinib is given two days after PNx surgery. Con received only the CMC that was solvent. Echocardiography is used to assess the morphometry and function of the heart at baseline (prehypoxia/presurgery), week 2, and week 6. The animals are put to sleep and their left and right ventricles' (LV and RV) pressures are measured using catheterization two and six weeks after surgery or hypoxia. |
| References |
| Molecular Formula |
C15H14N2O
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|---|---|
| Molecular Weight |
238.28
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| Exact Mass |
238.11
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| Elemental Analysis |
C, 75.61; H, 5.92; N, 11.76; O, 6.71
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| CAS # |
204005-46-9
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| Related CAS # |
(Z)-Semaxanib;194413-58-6
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| Appearance |
Yellow to orange solid powder
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| SMILES |
CC1=CC(=C(N1)/C=C\2/C3=CC=CC=C3NC2=O)C
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| InChi Key |
WUWDLXZGHZSWQZ-WQLSENKSSA-N
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| InChi Code |
InChI=1S/C15H14N2O/c1-9-7-10(2)16-14(9)8-12-11-5-3-4-6-13(11)17-15(12)18/h3-8,16H,1-2H3,(H,17,18)/b12-8-
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| Chemical Name |
(3Z)-3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one
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| Synonyms |
Sugen 5416; Sugen5416; Sugen-5416; semoxind; SU5416; SU-5416; SU 5416; Semaxanib
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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)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.49 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), suspension 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. Solubility in Formulation 2: 2.25 mg/mL (9.44 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 22.5 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. View More
Solubility in Formulation 3: 1% DMSO+30% polyethylene glycol+1% Tween 80: 30 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.1967 mL | 20.9837 mL | 41.9674 mL | |
| 5 mM | 0.8393 mL | 4.1967 mL | 8.3935 mL | |
| 10 mM | 0.4197 mL | 2.0984 mL | 4.1967 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00017316 | Completed | Drug: semaxanib Drug: thalidomide |
Melanoma (Skin) |
National Cancer Institute (NCI) |
March 2001 | Phase 2 |
| NCT00006002 | Completed | Drug: semaxanib Drug: dexamethasone |
Prostate Cancer | University of Chicago | June 2000 | Phase 2 |
| NCT00026260 | Completed | Drug: semaxanib | Cervical Cancer | Gynecologic Oncology Group | October 2003 | Phase 2 |
| NCT00005042 | Completed | Drug: semaxanib | Sarcoma | AIDS Malignancy Consortium | November 2000 | Phase 2 |
| NCT00005822 | Completed | Drug: semaxanib Drug: tamoxifen |
Breast Cancer | Case Comprehensive Cancer Center | April 2000 | Phase 1 |
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