1. Protein Tyrosine Kinase/RTK
  2. VEGFR

SU5416 (Synonyms: Semaxinib)

Cat. No.: HY-10374 Purity: 99.93%
Data Sheet SDS Handling Instructions

SU5416 is a potent and selective inhibitor of the VEGFR (Flk-1/KDR) that inhibits tyrosine kinase catalysis, and inhibits autophosphorylation of the Flk-1 receptor with an IC50 of 1.23±0.2 μM (n=4) using an ELISA-based biochemical kinase assay.

For research use only. We do not sell to patients.
SU5416 Chemical Structure

SU5416 Chemical Structure

CAS No. : 204005-46-9

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO $77 In-stock
10 mg $70 In-stock
50 mg $190 In-stock
100 mg $250 In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

Customer Review

Top Publications Citing Use of Products
  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

SU5416 is a potent and selective inhibitor of the VEGFR (Flk-1/KDR) that inhibits tyrosine kinase catalysis, and inhibits autophosphorylation of the Flk-1 receptor with an IC50 of 1.23±0.2 μM (n=4) using an ELISA-based biochemical kinase assay.

IC50 & Target

IC50: 1.23±0.2 μM (Flk-1 receptor)[1]

In Vitro

SU5416 inhibits VEGF-driven mitogenesis in a dose-dependent manner with an IC50 of 0.04±0.02 μM (n=3). In contrast, SU5416 blocked FGF-dependent mitogenesis of HUVECs with an IC50 of 50 μM (n=10). The selective activity of SU5416 on Flk-1 is supported by the fact that testing of SU5416 using NIH 3T3 cells overexpressing either the EGF or insulin receptors indicated a complete lack of activity (IC50>100 μM). This observation is confirmed by immunoblotting after ligand stimulation. An IC50 of 20.26±5.2 μM (n=7), which is about 20-fold less in potency on PDGF-dependent autophosphorylation, is observed when SU5416 is tested in NIH 3T3 cells overexpressing the human PDGF receptor β[1].

In Vivo

Daily administration of SU5416 (i.p., 3 mg/kg/day) inhibits the local growth of C6 tumors in the colon. A comparable level of growth inhibition (62% by day 16; P=0.001) is observed for tumors growing in the colon in comparison with ones growing in the hindflank region (54% by day 18; P=0.001). These results indicate that SU5416 could inhibit tumor growth at a site other than the subcutaneous implantation site, where the preexisting vasculature may be different[1]. Daily treatment with SU5416(25 mg/kg) results in a significantly lower tumor growth rate with tumor masses of up to 8% of that present in control animals by day 22 after implantation. Inhibition of tumor growth is clearly preceded by a marked reduction of the tissue area covered by the newly formed glioma microvasculature in the SU5416-treated group, indicating a reduced initial tumor vascularization[2].

Clinical Trial
NCT Number Sponsor Condition Start Date Phase
NCT00026377 University of Chicago|National Cancer Institute (NCI) Prostate Cancer November 2001 Phase 1
NCT00005931 SUGEN|NIH AIDS Clinical Trials Information Service Sarcoma, Kaposi|HIV Infections Phase 2
NCT00006155 National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) Fallopian Tube Neoplasm|Ovarian Cancer|Peritoneal Neoplasm August 2000 Phase 1
NCT00002226 SUGEN|NIH AIDS Clinical Trials Information Service Sarcoma, Kaposi|HIV Infections
View MoreCollapse
References
Preparing Stock Solutions
Concentration Volume (DMSO) Mass 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
Kinase Assay
[1]

Solubilized membranes from 3T3 Flk-1 cells are added to polystyrene ELISA plates that has been precoated with a monoclonal antibody that recognizes Flk-1. After an overnight incubation with lysate at 4°C, 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 peroxidase H is added to the wells. A stabilized form of 3,3′,5,5′-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. Parallel biochemical kinase assays are performed to measure autophosphorylation on EGFR and fibroblast growth factor receptor[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay

SU5416 is dissolved in DMSO and stored, and then diluted with appropriate media (DMSO<0.5%) before use[1]

3T3Her2 and 488G2M2 are NIH3T3 fibroblast cell lines engineered to overexpress Her2 and to express human PDGF-BB and human PDGF receptor β. Both cell lines are cultured in DMEM supplemented with 2% CS and 2 mM L-glutamine. C6, Calu 6, A375, A431, and SF767T are plated in their respective growth medium at 2×103 cells/100 μL/well in 96-well, flat-bottomed plates. SU5416 is serially diluted in media containing DMSO (<0.5%) and added to cultures of tumor cells 1 day after the initiation of culture. Cell growth is measured after 96 h using the sulforhodamine B method. IC50s are calculated by curve fitting using four-parameter analysis[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1][3]

SU5416 is dissolved in DMSO (Mice)[1].
SU5416 is dissolved in carboxymethylcellulose (CMC) (Rat)[3].

Mice[1]
Female BALB/c nu/nu mice (20-22 g; 12 weeks of age) are anesthesized using a mixture of xylazine (5 mg/kg) and ketamine (100 mg/kg). Aseptic technique is used during this surgical procedure. A small midline incision (1 cm) is made in the abdomen directly over the colon. C6 cells are implanted (0.5×106 cells/animal) under the serosa of the colon using a 27-gauge needle. After implantation, all exposed sections of the intestine are returned into the abdominal cavity. The peritoneum and skin are closed using a 6.0 surgical suture and wound clips. The wound clips are removed 7 days after surgery. Animals are treated once daily with a 50 μL i.p. bolus injection of either SU5416 or DMSO, beginning 1 day after implantation. Approximately 13-16 days after implantation, animals are euthanized, and local tumor growth on the colon is quantitated either by weighing the tumors or by measuring the tumors using venier calipers. Tumor volumes are calculated as the product of length×width×height.
Rat[3]
Male Sprague Dawley rats (n=60, 6-8 wk) are randomly divided among five groups: control (Con), SU5416 (SU), pneumonectomy (PNx), SU5416+hypoxia (SuHx), and SU5416+PNx (SuPNx). The SuHx protocol is employed. Briefly, animals are injected with SU5416 (25 mg/kg) dissolved in carboxymethylcellulose (CMC) and exposed to hypoxia (10%) for 4 wk followed by re-exposure to normoxia. PNx animals underwent a left pneumonectomy. Two days following PNx surgery an injection of SU5416 is administered (25 mg/kg). The Con group received only the solvent CMC. Echocardiography is utilized at baseline (prehypoxia/presurgery), week 2, and week 6 to determine cardiac morphometry and function. Two and six weeks postsurgery/posthypoxia animals are anesthetized and right ventricle (RV) and left ventricle (LV) pressure measurements via catheterization are performed. Animals are killed via exsanguination, and organs are weighed and processed for analysis. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
M.Wt

238.28

Formula

C₁₅H₁₄N₂O

CAS No.

204005-46-9

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: 22.5 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.93%

Inquiry Online

Your information is safe with us. * Required Fields.

Product name

 

Salutation

Applicant name *

 

Email address *

Phone number

 

Organization name *

Country *

 

Requested quantity *

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
SU5416
Cat. No.:
HY-10374
Quantity: