SU11274

Catalog No.S1080 Batch:S108001

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Technical Data

Formula

C28H30CIN5O4S
Molecular Weight 568.09 CAS No. 658084-23-2
Solubility (25°C)* In vitro DMSO 92 mg/mL (161.94 mM)
Ethanol 2 mg/mL (3.52 mM)
Water Insoluble
In vivo (Add solvents to the product individually and in order)
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5% DMSO 40% PEG300 5%Tween80 50%ddH2O

Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.

 4.600mg/ml (8.10mM) Taking the 1 mL working solution as an example, add 50 μL of 92 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; 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. 
* <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 SU11274 (PKI-SU11274) is a selective Met (c-Met) inhibitor with IC50 of 10 nM in cell-free assays, no effects on PGDFRβ, EGFR or Tie2. SU11274 induces autophagy, apoptosis and cell cycle arrest.
Targets
Met [1]
(Cell-free assay)
0.01 μM
In vitro SU11274 exhibits greater than 50-fold selectivity for Met versus Flk and more than 500 times selectivity versus other tyrosine kinases such as FGFR-1, c-src, PDGFbR, and EGFR. SU11274 inhibits the phosphorylation of key regulators of the PI3K pathway, including AKT, FKHR, or GSK3β. SU11274 treatment inhibits the growth of TPR-MET-transformed BaF3 cells in a dose-dependent manner with IC50 of <3 μM in the absence of interleukin 3, without growth inhibition of BaF3 cells transformed by other oncogenic tyrosine kinases, including BCR-ABL, TEL-JAK2, TEL-ABL, and TEL-PDGFβR. In addition to cell growth, SU11274 treatment significantly inhibits the migration of BaF3. TPR-MET cells by 44.8% and 80% at 1 μM and 5 μM, respectively. SU11274 inhibits HGF-dependent phosphorylation of Met as well as HGF-dependent cell proliferation and motility with an IC50 of 1-1.5 μM. In H69 and H345 cells which have functional Met receptor, SU11274 inhibits the HGF-induced cell growth with IC50 of 3.4 μM and 6.5 μM, respectively. SU11274 induces G1 cell cycle arrest with cells in G1 phase increased from 42.4% to 70.6% at 5 μM, and induces caspase-dependent apoptosis by 24% at 1 μM. [2] SU11274 inhibits cell viability in c-Met-expressing non-small cell lung cancer (NSCLC) cells with IC50 values of 0.8-4.4 μM, and abrogates hepatocyte growth factor-induced phosphorylation of c-Met and its downstream signaling. [3]

Protocol (from reference)

Kinase Assay:[1]
  • In vitro Met kinase assay

    A chimeric protein is constructed containing the cytoplasmic domain of human c-Met fused to Glutathione S-transferase (GST) and expressed in SF9 cells. The c-Met kinase GST-fusion protein is used for an ELISA-based Met biochemical assay using the random copolymer poly(Glu:Tyr) (4:1) immobilized on microtiter plates as a substrate. IC50 value is determined with various concentrations of SU11274 in a buffer containing 5 μM ATP and 10 mM MnCl2, 50 mM HEPES (pH 7.5), 25 mM NaCl, 0.01% BSA, and 0.1 mM Na orthovanadate. The kinase reaction is performed for 5 minutes at room temperature. The extent of substrate phosphorylation is measured using horseradish peroxidase-conjugated anti-pTyr antibodies.
Cell Assay:[2]
  • Cell lines

    BaF3.TPR-MET, H69 and H345 cells

  • Concentrations

    Dissolved in DMSO, final concentrations ~10 μM

  • Incubation Time

    24, 48, and 72 hours

  • Method

    Cells are exposed to various concentrations of SU11274 in the presence or absence of HGF for 24, 48, and 72 hours. The number of viable cells is determined using the MTT assay or trypan blue exclusion. Cell Cycle and apoptosis are measured by fluorescence-activated cell sorter analysis via propidium iodide staining and Annexin V-positive staining, respectively.

References

  • https://pubmed.ncbi.nlm.nih.gov/14617781/
  • https://pubmed.ncbi.nlm.nih.gov/14500382/
  • https://pubmed.ncbi.nlm.nih.gov/15735036/

Customer Product Validation

Effect of crizotinib, tivantinib, and SU11274 on levels of c-MET phosphorylation and downstream signaling pathway in SW1736 and TL3 thyroid cancer cells. Cells were prestarved in culture medium containing 0.5% FBS (24 hour) ?either crizotinib or tivantinib (0.1, 1.0, and 10 umol/L) or SU11274 (10 umol/L), and stimulated with 20 ng/mL recombinant human HGF for 10 minutes before lysates were made for Western blotting. A series of c-MET downstream signaling pathway proteins and phosphor proteins were detected using Western blotting. β-Actin was used as a loading balance control.

Data from [ Mol Cancer Ther , 2014 , 13(1), 134-43 ]

HLMVECs grown to -95% confluence on slide chambers were pretreated with 1 uM SU11274 for 1 h prior to stimulation with HGF (20 ng/ml) for 15 min. Cells were washed, fixed, and stained for actin and cortactin co-localization in lamellipodia as described under "Experimental Procedures." Nuclei were stained with DAPI. Shown are representative immunofluorescence images from three independent experiments. Actin and cortactin co-localization in lamellipodia was quantified using image analysis as described under "Experimental Procedures."

Data from [ J Biol Chem , 2014 , 289(19), 13476-91 ]

Human umbilical vein endothelial cells (HUVECs) were stained for cortactin (green)/vinculin (red; top) and for zyxin (green)/actin (red; bottom). On RCαβ treatment for 30 to 40 minutes, vinculin disappeared from large focal adhesions underneath the cell body, whereas it appeared in small focal contacts around the cell perimeter. In addition, cortactin was found in the cortical actin network within nascent lamellipodia. Furthermore, zyxin, a marker of focal adhesions, and stress fibers disappeared on RCαβ treatment. Pretreatment of HUVECs with 10 umol/L SU11274 reduced the effect of 200 nmol/L RCαβ, whereas 200 ng/mL hepatocyte growth factor (HGF) elicited similar responses to RCαβ, indicating a signaling path involving cMet. Scale bars, 10 um.

Data from [ Arterioscler Thromb Vasc Biol , 2013 , 33(3), 544-54 ]

Inhibition of c-MET sensitizes PTEN deficient tumor cells to EGFR TKI-induced apoptosis. PTEN deficient TGFα-EGFR<sup>WT</sup>;InkΔ2/3-/-;PTEN<sup>lox</sup> GBM tumor cells were treated with gefitinib (10 uM) and/or the c-MET kinase inhibitor SU11274 (10 uM). Immunoblot analysis of total cell lysates from TGFα-EGFR<sup>WT</sup>;InkΔ2/3-/-;PTEN<sup>lox</sup> GBM tumor cells treated with the indicated inhibitors using c-MET and c-MET phosphotyrosine 1234,1235 antibodies. Anti β-tubulin probing is used as an internal loading control.

Data from [ Oncogene , 2012 , 31(25), 3039-50 ]

Selleck's SU11274 Has Been Cited by 69 Publications

Inhibition of TFF3 synergizes with c-MET inhibitors to decrease the CSC-like phenotype and metastatic burden in ER+HER2+ mammary carcinoma [ Cell Death Dis, 2025, 16(1):76] PubMed: 39920140
Establishment and characterization of a new human gallbladder cancer cell line, OCUG-2 [ World J Exp Med, 2025, 15(2):100443] PubMed: 40546672
The anti-tumor effects of AZD4547 on ovarian cancer cells: differential responses based on c-Met and FGF19/FGFR4 expression [ Cancer Cell Int, 2024, 24(1):43] PubMed: 38273381
Establishing a new human lung squamous cell carcinoma cell line, OMUL-1, expressing insulin-like growth factor 1 receptor and programmed cell death ligand 1 [ Thorac Cancer, 2024, 10.1111/1759-7714.15488] PubMed: 39552203
Epithelial cell adhesion molecule (EpCAM) regulates HGFR signaling to promote colon cancer progression and metastasis [ J Transl Med, 2023, 21(1):530] PubMed: 37543570
Epithelial cell adhesion molecule (EpCAM) regulates HGFR signaling to promote colon cancer progression and metastasis [ J Transl Med, 2023, 21(1):530] PubMed: 37543570
Met-signaling Controls Dendritic Cell Migration in Skin by Regulating Podosome Formation and Function [ J Invest Dermatol, 2023, S0022-202X(23)00100-8] PubMed: 36813160
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
Resistance to tyrosine kinase inhibitors promotes renal cancer progression through MCPIP1 tumor-suppressor downregulation and c-Met activation [ Cell Death Dis, 2022, 13(9):814] PubMed: 36138026
β2-adrenergic receptor promotes liver regeneration partially through crosstalk with c-met [ Cell Death Dis, 2022, 13(6):571] PubMed: 35760785

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