SU11274

Catalog No.S1080

SU11274 is a selective Met inhibitor with IC50 of 10 nM in cell-free assays, no effects on PGDFRβ, EGFR or Tie2.

Price Stock Quantity  
USD 300 In stock
USD 70 In stock
USD 120 In stock
USD 470 In stock
Bulk Inquiry

Massive Discount Available

Free Overnight Delivery on all orders over $ 500.

SU11274 Chemical Structure

SU11274 Chemical Structure
Molecular Weight: 568.09

Validation & Quality Control

6 customer reviews :

Quality Control & MSDS

Related Compound Libraries

c-Met Inhibitors with Unique Features

  • Non-specific c-Met Inhibitor

    BMS-777607 C-Met, IC50=3.9 nM;Axl, IC50=1.1 nM; Ron, IC50=1.8 nM; Tyro3, IC50=4.3 nM.

  • Most Potent c-Met Inhibitor

    INCB28060 C-Met, IC50=0.13 nM.

  • FDA-approved c-Met Inhibitor

    Crizotinib (PF-02341066) Approved by FDA for non-small cell lung carcinoma (NSCLC).

  • Newest c-Met Inhibitor

    EMD 1214063 Potent and selective c-Met inhibitor with IC50 of 4 nM, >200-fold selective for c-Met than IRAK4, TrkA, Axl, IRAK1, and Mer.

Product Information

  • Compare c-Met Inhibitors
    Compare c-Met Products
  • Research Area
  • Inhibition Profile
  • SU11274 Mechanism

Product Description

Biological Activity

Description SU11274 is a selective Met inhibitor with IC50 of 10 nM in cell-free assays, no effects on PGDFRβ, EGFR or Tie2.
Targets Met [1]
(Cell-free assay)
Flk1 [1]
(Cell-free assay)
RON [1]
(Cell-free assay)
FGFR1 [1]
(Cell-free assay)

 View  More

IC50 0.01 μM 1.25 μM 4.0 μM 8.5 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]
In vivo
Features

Protocol(Only for 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.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Wang X, et al. Mol Cancer Ther, 2003, 2(11):1085-1092.

[2] Sattler M, et al. Cancer Res, 2003, 63(17), 5462-5469.

view more

Chemical Information

Download SU11274 SDF
Molecular Weight (MW) 568.09
Formula

C28H30CIN5O4S

CAS No. 658084-23-2
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms PKI-SU11274
Solubility (25°C) * In vitro DMSO 92 mg/mL (161.94 mM)
Ethanol 2 mg/mL (3.52 mM)
Water <1 mg/mL (<1 mM)
In vivo 30% PEG400+0.5% Tween80+5% propylene glycol 30 mg/mL
* <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.
Chemical Name (Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-(1-methylpiperazine-4-carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxoindoline-5-sulfonamide

Customer Product Validation(6)


Click to enlarge
Rating
Source Oncogene 2012 31(25), 3039-50. SU11274 purchased from Selleck
Method Immunoblot analysis
Cell Lines TGFα-EGFRWT, InkΔ2/3-/-, PTENlox GBM tumor cells
Concentrations 10 uM
Incubation Time 72 h
Results As such, we reasoned that co-treatment of TGFα-EGFRWT;InkΔ2/3−/−;PTENlox tumor cells with gefitinib and the MET inhibitor SU11274 may sensitize these cells to apoptosis. Treatment of TGFα-EGFRWT;InkΔ2/3−/−;PTENlox tumor cell cultures with both gefitinib and SU11274 robustly abrogated the levels of phospho MET Tyr1234/1235, indicating a complete inhibition of MET activity.

Click to enlarge
Rating
Source Arterioscler Thromb Vasc Biol 2013 33(3), 544-54. SU11274 purchased from Selleck
Method Immunofluorescence
Cell Lines RCαβ-treated HUVECs
Concentrations 10 uM
Incubation Time 1 h
Results The focal adhesion marker zyxin, which was clearly localized to focal adhesions before RCαβ treatment, was not detected in any well-defined structures within RCαβ-treated HUVECs. Because focal adhesions are the docking sites for actin stress fibers, their loss was accompanied by the destruction of actin stress fibers that span the cell body and transmit tensile forces. SU11274 reverted the effects of RCαβ on HUVECS, most prominently the relocation of vinculin and the percentage of cortactin-positive lamellipodia. HGF induced similar effects to RCαβ, additionally suggesting that RCαβ acts via cMet signaling.

Click to enlarge
Rating
Source Mol Cancer Ther 2014 13(1), 134-43. SU11274 purchased from Selleck
Method Immunoblot analysis
Cell Lines SW1736, TL3 thyroid cancer cells
Concentrations 10 uM
Incubation Time 24 h
Results Two thyroid cancer cell lines (SW1736 and TL3 cells), who were growth inhibited by both c-MET inhibitors, were serum-starved (24 hours) followed by 10 minutes stimulation with 20 ng/mL HGF. SU11274 (another ATP-competitive c-MET inhibitor, 10 umol/L) also inhibited P-MET, P-AKT, and P-STAT3 in both cells. Phosphorylation of ERK and 4E-BP1 (indicator of the activation of mTOR pathways) was not significantly altered by either inhibitor. Crizotinib was 10- to 100-fold more potent than tivantinib in blocking c-MET phosphorylation.

Click to enlarge
Rating
Source J Biol Chem 2014 289(19), 13476-91. SU11274 purchased from Selleck
Method Immunofluorescence
Cell Lines Human lung microvascular endothelial cells
Concentrations 1 uM
Incubation Time 1 h
Results SU11274 significantly attenuated HGF-induced actin and cortactin redistribution to cell periphery and their co-localization in lamellipodia. Further, inhibition of c-Met phosphorylation with SU11274 reduced HGF-induced hydrogen peroxide accumulation in lamellipodia of HLMVECs.

Click to enlarge
Rating
Source Cancer Sci 2011 102, 2164-71. SU11274 purchased from Selleck
Method qRT-PCR analysis
Cell Lines HSC3 cells
Concentrations 10 mM
Incubation Time 6 h
Results Downregulation of miR-200c and miR-27b by HGF stimulation was almost completely inhibited by adding MET kinase-specific inhibitor SU11274 before HGF stimulation.

Click to enlarge
Rating
Source Dr. Zhang of Tianjin Medical University. SU11274 purchased from Selleck
Method Western blot
Cell Lines MDA-MB-231 cells
Concentrations 0-20 μM
Incubation Time
Results SU11274 treatment resulted in a reduction of c-Met, AKT and MAPK phosphorylation in MDA-MB-231 cells.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

* Indicates a Required Field

Related c-Met Products

  • NPS-1034

    NPS-1034 is a dual Met/Axl inhibitor with IC50 of 48 nM and 10.3 nM, respectively.

  • Erlotinib

    Erlotinib is an EGFR inhibitor with IC50 of 2 nM, >1000-fold more sensitive for EGFR than human c-Src or v-Abl.

  • R428 (BGB324)

    R428 (BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective).

  • Crizotinib (PF-02341066)

    Crizotinib (PF-02341066) is a potent inhibitor of c-Met and ALK with IC50 of 11 nM and 24 nM in cell-based assays, respectively.

  • Foretinib (GSK1363089)

    Foretinib (GSK1363089) is an ATP-competitive inhibitor of HGFR and VEGFR, mostly for Met and KDR with IC50 of 0.4 nM and 0.9 nM in cell-free assays. Less potent against Ron, Flt-1/3/4, Kit, PDGFRα/β and Tie-2, and little activity to FGFR1 and EGFR. Phase 2.

  • Capmatinib (INCB28060)

    Capmatinib (INCB28060) is a novel, ATP-competitive inhibitor of c-MET with IC50 of 0.13 nM in a cell-free assay, inactive against RONβ, as well as EGFR and HER-3. Phase 1.

    Features:Inactive against RONβ, another member of the c-MET RTK family, as well as EGFR and HER-3 (members of the EGFR RTK family).

  • Tivantinib (ARQ 197)

    Tivantinib (ARQ 197) is the first non-ATP-competitive c-Met inhibitor with Ki of 0.355 μM in a cell-free assay, little activity to Ron, and no inhibition to EGFR, InsR, PDGFRα or FGFR1/4. Phase 3.

    Features:The first selective c-Met inhibitor to be advanced into human clinical trials.

  • PHA-665752

    PHA-665752 is a potent, selective and ATP-competitive c-Met inhibitor with IC50 of 9 nM in cell-free assays, >50-fold selectivity for c-Met than RTKs or STKs.

  • BMS-777607

    BMS-777607 is a Met-related inhibitor for c-Met, Axl, Ron and Tyro3 with IC50 of 3.9 nM, 1.1 nM, 1.8 nM and 4.3 nM in cell-free assays, 40-fold more selective for Met-related targets versus Lck, VEGFR-2, and TrkA/B, and more than 500-fold greater selectivity versus all other receptor and non receptor kinases. Phase 1/2.

    Features:A potent inhibitor of the Met family, and >40-fold selectivity vs. Lck, VEGFR2, and TrkA/B and >500-fold selective vs. other receptor and non-receptor kinases.

  • PF-04217903

    PF-04217903 is a selective ATP-competitive c-Met inhibitor with IC50 of 4.8 nM in A549 cell line, susceptible to oncogenic mutations (no activity to Y1230C mutant). Phase 1.

Recently Viewed Items

Tags: buy SU11274 | SU11274 supplier | purchase SU11274 | SU11274 cost | SU11274 manufacturer | order SU11274 | SU11274 distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Contact Us