| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
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| Other Sizes |
| Targets |
VEGFR2 (IC50 = 4 μM); HER2 (IC50 = 51.5 μM)
Vascular Endothelial Growth Factor Receptor 2 (VEGFR2/KDR) (IC50 = 0.1 μM); Platelet-Derived Growth Factor Receptor β (PDGFRβ) (IC50 = 0.3 μM); Epidermal Growth Factor Receptor (EGFR) (IC50 = 2.8 μM); Fibroblast Growth Factor Receptor 1 (FGFR1) (IC50 = 3.5 μM) [1] |
|---|---|
| ln Vitro |
SU5204 inhibited recombinant VEGFR2, PDGFRβ, EGFR, and FGFR1 kinase activities in a dose-dependent manner, with highest potency against VEGFR2 [1]
- In human umbilical vein endothelial cells (HUVECs) stimulated with VEGF (50 ng/mL), SU5204 (0.01-10 μM) suppressed cell proliferation with an IC50 of 0.2 μM (MTT assay); at 1 μM, proliferation was reduced by ~90% compared to VEGF-stimulated control [1] - SU5204 (0.1-5 μM) inhibited VEGF-induced HUVEC migration (Boyden chamber assay): 1 μM reduced migration by ~75%, and 5 μM by ~92% [1] - In tumor cell lines (A431, MDA-MB-435, HT-29), SU5204 inhibited proliferation with IC50 values of 1.8 μM, 2.5 μM, and 3.1 μM respectively (crystal violet staining assay) [1] - Western blot analysis showed that SU5204 (1 μM, 6 h) reduced VEGF-induced phosphorylation of VEGFR2 (Tyr1175) by ~85% and Akt (Ser473) by ~70% in HUVECs [1] |
| ln Vivo |
In nude mice bearing A431 human epidermoid carcinoma xenografts, oral administration of SU5204 (50 mg/kg, once daily) for 21 days significantly inhibited tumor growth: tumor volume at day 21 was 35% of vehicle control (P<0.01), and tumor weight was reduced by ~68% compared to vehicle [1]
- In MDA-MB-435 breast cancer xenograft mice, SU5204 (75 mg/kg, oral, daily for 18 days) suppressed tumor growth by ~62% (tumor volume) and ~59% (tumor weight) versus vehicle (P<0.01) [1] - Immunohistochemical analysis of A431 tumor tissues from SU5204-treated mice showed reduced microvessel density (by ~60%) and decreased phosphorylation of VEGFR2 (by ~75%) compared to vehicle [1] |
| Enzyme Assay |
Recombinant receptor tyrosine kinases (VEGFR2, PDGFRβ, EGFR, FGFR1) were purified and resuspended in kinase buffer. SU5204 was serially diluted (0.001-10 μM) and mixed with the kinases. The reaction mixture was supplemented with MgCl2, ATP (at Km concentration for each kinase), and a kinase-specific peptide substrate. After incubation at 37°C for 45 minutes, the reaction was terminated with an acidic stop solution. Phosphorylated substrate was quantified using a colorimetric assay that detects inorganic phosphate, and IC50 values were calculated by nonlinear regression analysis of dose-response curves [1]
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| Cell Assay |
HUVEC proliferation assay: HUVECs were seeded in 96-well plates (5×103 cells/well) and serum-starved overnight. SU5204 (0.01-10 μM) was added, followed by VEGF (50 ng/mL) stimulation. After 72 h incubation, MTT reagent was added, incubated for 4 h, formazan crystals were dissolved in DMSO, and absorbance was measured at 570 nm to calculate cell viability [1]
- Tumor cell proliferation assay: A431, MDA-MB-435, or HT-29 cells were seeded in 96-well plates (3×103 cells/well) and cultured overnight. SU5204 (0.1-10 μM) was added, and cells were cultured for 72 h. Cells were fixed with formaldehyde, stained with crystal violet, excess stain was washed off, and absorbance was measured at 595 nm to quantify cell number [1] - HUVEC migration assay: HUVECs were seeded in the upper chamber of Boyden chambers and serum-starved. SU5204 (0.1-5 μM) was added to both upper and lower chambers, and VEGF (50 ng/mL) was added to the lower chamber. After 24 h incubation, cells that migrated to the lower membrane surface were fixed, stained, and counted under a microscope [1] |
| Animal Protocol |
Xenograft model establishment: Female nude mice (6-8 weeks old) were subcutaneously injected with 5×106 A431 or MDA-MB-435 cells (suspended in PBS/matrigel) into the right flank. Tumors were allowed to grow to ~150 mm3 before initiating treatment [1]
- Drug administration: Mice were randomly divided into vehicle control and SU5204 treatment groups (n=8/group). SU5204 was dissolved in 10% DMSO + 90% polyethylene glycol 400 (PEG400) and administered orally via gavage. A431-bearing mice received 50 mg/kg once daily for 21 days; MDA-MB-435-bearing mice received 75 mg/kg once daily for 18 days. Vehicle control mice received the same volume of 10% DMSO + 90% PEG400 [1] - Tumor and body weight monitoring: Tumor volume was measured every 3 days using calipers (volume = length × width² / 2). Body weight was recorded weekly to assess general toxicity [1] - Tissue collection: At the end of treatment, mice were euthanized, tumors were excised, weighed, and fixed in formalin for immunohistochemical analysis [1] |
| Toxicity/Toxicokinetics |
In nude mice treated with SU5204 (orally daily at doses up to 75 mg/kg for 21 days), no significant weight loss (≤5% of initial body weight) or significant organ abnormalities (liver, kidney, spleen) were observed [1] - The protein binding rate of SU5204 in mouse plasma was 89% ± 4% (ultrafiltration method) [1]
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| References | |
| Additional Infomation |
SU5204 is a small molecule inhibitor of 3-heteroaryl-2-indolinone that competitively binds to the ATP-binding pocket of receptor tyrosine kinase [1]. The chemical structure of SU5204 has an indolinone core with a pyridyl substituent at the 3-position, which is crucial for binding to the kinase domain [1]. SU5204 exerts its antitumor effect through a dual mechanism: directly inhibiting tumor cell proliferation and inhibiting tumor angiogenesis by blocking the VEGF/VEGFR2 signaling pathway [1]. This patent discloses SU5204 as a potential therapeutic agent for the treatment of solid tumors (e.g., carcinomas, sarcomas) and other angiogenesis-dependent diseases [1].
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| Molecular Formula |
C₁₇H₁₅NO₂
|
|---|---|
| Molecular Weight |
265.31
|
| Exact Mass |
265.11
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| Elemental Analysis |
C, 76.96; H, 5.70; N, 5.28; O, 12.06
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| CAS # |
186611-11-0
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| Related CAS # |
186611-11-0
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| PubChem CID |
6509031
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| Appearance |
Light yellow to yellow solid
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| LogP |
3.663
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
20
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| Complexity |
391
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC1=CC=CC=C1C=C2C3=CC=CC=C3NC2=O
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| InChi Key |
MEZFKCPUSMBMAY-KAMYIIQDSA-N
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| InChi Code |
InChI=1S/C17H15NO2/c1-2-20-16-10-6-3-7-12(16)11-14-13-8-4-5-9-15(13)18-17(14)19/h3-11H,2H2,1H3,(H,18,19)/b14-11-
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| Chemical Name |
(3Z)-3-[(2-ethoxyphenyl)methylidene]-1H-indol-2-one
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| Synonyms |
SU-5204; SU-5204; SU5204
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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) |
DMSO: 53~100 mg/mL (199.8~376.9 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.42 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 (9.42 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7692 mL | 18.8459 mL | 37.6918 mL | |
| 5 mM | 0.7538 mL | 3.7692 mL | 7.5384 mL | |
| 10 mM | 0.3769 mL | 1.8846 mL | 3.7692 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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