SU11274

Catalog No.S1080 Batch:S108001

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
* <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.)

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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.

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

Customer Product Validation

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

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

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

: Data from [Data independently produced by Oncogene, 2012, 31(25), 3039-50]

Selleck's SU11274 has been cited by 65 publications

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
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
Anosmin-1-Like Effect of UMODL1/Olfactorin on the Chemomigration of Mouse GnRH Neurons and Zebrafish Olfactory Axons Development [ Front Cell Dev Biol, 2022, 10:836179]	PubMed: 35223856
MET Inhibition Sensitizes Rhabdomyosarcoma Cells to NOTCH Signaling Suppression [ Front Oncol, 2022, 12:835642]	PubMed: 35574376
Fis1 phosphorylation by Met promotes mitochondrial fission and hepatocellular carcinoma metastasis [ Signal Transduct Target Ther, 2021, 6(1):401]	PubMed: 34848680

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SHIPPING AND STORAGE
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