Semaxanib (SU5416)

Catalog No.S2845 Batch:S284503

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Technical Data

Formula

C15H14N2O
Molecular Weight 238.28 CAS No. 204005-46-9
Solubility (25°C)* In vitro DMF 100 mg/mL (419.67 mM)
DMSO 20 mg/mL (83.93 mM)
Ethanol 4 mg/mL (16.78 mM)
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
0.5mg/ml Taking the 1 mL working solution as an example, add 50 μL of 10 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
10% DMF 40% PEG 300 5%Tween80 45%ddH2O
3.3mg/ml Taking the 1 mL working solution as an example, add 100μL of 33mg/ml clarified DMF stock solution to 400μL of PEG300, mix evenly to clarify it; add 50μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 450μL of ddH2O to adjust the volume to 1mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description Semaxanib (SU5416, semaxinib) is a potent and selective VEGFR(Flk-1/KDR) inhibitor with IC50 of 1.23 μM, 20-fold more selective for VEGFR than PDGFRβ, lack of activity against EGFR, InsR and FGFR. Phase 3.
Targets
VEGFR2/Flk1 [1]
(Cell-free assay)
1.23 μM
In vitro Semaxanib inhibits VEGF-dependent phosphorylation of the Flk-1 receptor in Flk-1-overexpressing NIH 3T3 cells with IC50 of 1.04 μM. Semaxanib inhibits PDGF-dependent autophosphorylation in NIH 3T3 cells with IC50 of 20.3 μM. Semaxanib inhibits VEGF- and FGF-driven mitogenesis in a dose-dependent manner with IC50 of 0.04 and 50 μM, respectively. Semaxanib treatment has no effect on the in vitro growth of C6 glioma, Calu 6 lung carcinoma, A375 melanoma, A431 epidermoid carcinoma, and SF767T glioma cells (all IC50s > 20 μM). [1]
In vivo Semaxanib dose-related inhibits growth of A375 tumor in vivo. A >85% inhibition of subcutaneous tumor growth is observed with daily i.p. administration of SU5416 in DMSO at Semaxanib, without measurable toxicity. Semaxanib shows broad spectrum antitumor activity. SU5416 significantly inhibits the subcutaneous growth of 8 of 10 tumor lines tested (A431, Calu-6, C6, LNCAP, EPH4-VEGF, 3T3HER2, 488G2M2 and SF763T cells) with an average mortality rate of 2.5%. [1] Semaxanib (25 mg/kg/day) displays potent antiangiogenic activity, resulting in a significant reduction of both the total and functional vascular density of the tumor microvasculature. [2]

Protocol (from reference)

Kinase Assay:[1]
  • Biochemical kinase assays

    Solubilized membranes from 3T3 Flk-1 cells are added to polystyrene ELISA plates that had been precoated with a monoclonal antibody that recognizes Flk-1. After an overnight incubation with lysate at 4 ℃, serial dilutions of SU5416 are added to the immunolocalized receptor. To induce autophosphorylation of the receptor, various concentrations of ATP are added to the ELISA plate wells containing serially diluted solutions of SU5416. The autophosphorylation is allowed to proceed for 60 min at room temperature and then stopped with EDTA. The amount of phosphotyrosine present on the Flk-1 receptors in the individual wells is determined by incubating the immunolocalized receptor with a biotinylated monoclonal antibody directed against phosphotyrosine. After removal of the unbound anti-phosphotyrosine antibody, avidin-conjugated horseradish pero-idase H is added to the wells. A stabilized form of 3,3 9,5,5 9-tetramethyl benzidine dihydrochloride and H2O2 is added to the wells. The color readout of the assay is allowed to develop for 30 min, and the reaction is stopped with H2SO4.
Cell Assay:[1]
  • Cell lines

    HUVECs

  • Concentrations

    ~100 μM

  • Incubation Time

    2 days

  • Method

    HUVECs are plated in 96-well, flat-bottomed plates (1×104 cells/100 μL/well) in F-12K media containing 0.5% heat-inactivated FBS and cultured at 37 ℃ for 24 h to quiesce the cells. Serial dilutions of compounds prepared in medium containing 1% DMSO are then added for 2 h, followed by the addition of mitogenic concentrations of either VEGF at 5 ng/mL or 20 ng/mL or acidic fibroblast growth factor at 0.25–5 ng/mL in media. The final concentration of DMSO in the assay is 0.25%. After 24 h, either [3H]thymidine (1 μCi/well) or BrdUrd is added, and the cell monolayers are incubated for another 24 h. The uptake of either [3H]thymidine or BrdUrd into cells is quantitated using a liquid scintillation counter or a BrdUrd ELISA, respectively.
Animal Study:[1]
  • Animal Models

    Human melanoma xenografts A375

  • Dosages

    25 mg/kg

  • Administration

    i.p. daily

Customer Product Validation

Data from [Data independently produced by , , Sci Rep, 2016, 6:19304. ]

Data from [Data independently produced by , , Angiogenesis, 2017, 20(4):629-640]

Data from [Data independently produced by , , Int Forum Allergy Rhinol, 2017, 7(10):973-979]

Selleck's Semaxanib (SU5416) has been cited by 17 publications

A novel twelve-gene signature to predict neoadjuvant chemotherapy response and prognosis in breast cancer [ Front Immunol, 2022, 13:1035667] PubMed: 36341435
VEGF Modulates Neurogenesis and Microvascular Remodeling in Epileptogenesis After Status Epilepticus in Immature Rats [ Front Neurol, 2021, 12:808568] PubMed: 35002944
PKR deficiency alleviates pulmonary hypertension via inducing inflammasome adaptor ASC inactivation [ Pulm Circ, 2021, 11(4):20458940211046156] PubMed: 34540200
Uncovering mutation-specific morphogenic phenotypes and paracrine-mediated vessel dysfunction in a biomimetic vascularized mammary duct platform [ Nat Commun, 2020, 11(1):3377] PubMed: 32632100
RhoJ integrates attractive and repulsive cues in directional migration of endothelial cells [ EMBO J, 2020, 39(12):e102930] PubMed: 32347571
Activation of inflammasomes by tyrosine kinase inhibitors of vascular endothelial growth factor receptor: Implications for VEGFR TKIs-induced immune related adverse events [ Toxicol In Vitro, 2020, 71:105063] PubMed: 33271325
Supramolecular Engineering of Molecular Inhibitors in an Adaptive Cytotoxic Nanoparticle for Synergistic Cancer Therapy [ ACS Appl Mater Interfaces, 2019, 101021/acsami9b20178] PubMed: 31816241
Periarticular Mesenchymal Progenitors Initiate and Contribute to Secondary Ossification Center Formation During Mouse Long Bone Development [ Stem Cells, 2019, 37(5):677-689] PubMed: 30681752
Epidermal-specific deletion of TC-PTP promotes UVB-induced epidermal cell survival through the regulation of Flk-1/JNK signaling [ Cell Death Dis, 2018, 9(7):730] PubMed: 29955047
3D endothelial cell spheroid/human vitreous humor assay for the characterization of anti-angiogenic inhibitors for the treatment of proliferative diabetic retinopathy [Rezzola S, et al. Angiogenesis, 2017, 20(4):629-640] PubMed: 28905243

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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