Orantinib (SU6668)

製品コードS1470 バッチS147003

印刷

化学情報

Chemical Structure Synonyms TSU-68 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C18H18N2O3
分子量 310.35 CAS No. 252916-29-3
Solubility (25°C)* 体外 DMSO 62 mg/mL (199.77 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
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.
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Orantinib (TSU-68, SU6668) has greatest potency against PDGFR autophosphorylation with Ki of 8 nM in a cell-free assay, but also strongly inhibits Flk-1 and FGFR1 trans-phosphorylation, little activity against IGF-1R, Met, Src, Lck, Zap70, Abl and CDK2; does not inhibit EGFR. Phase 3.
in vitro Orantinib (SU6668) is a competitive inhibitor, with regard to ATP, to Flk-1/KDR trans-phosphorylation, FGFR1 trans-phosphorylation, and PDGFRβ kinases autophosphorylation. This compound (0.03-10 μM) inhibits tyrosine phosphorylation of KDR in VEGF stimulated HUVECs. It also inhibits PDGF-stimulated PDGFRβ tyrosine phosphorylation in NIH-3T3 cells overexpressing PDGFRβ at a minimum concentration of 0.03-0.1 μM. TSU-68 inhibits acidic FGF-induced phosphorylation of the FGFR1 substrate 2 at 10 μM and higher. However, it (up to 100 μM) has no effect on EGF-stimulated EGFR tyrosine phosphorylation in NIH-3T3 cells overexpressing EGFR. It inhibits VEGF-driven and FGF-driven mitogenesis of HUVECs with mean IC50 of 0.34 μM and 9.6 μM, respectively. [1] In human myeloid leukemia MO7E cells, it inhibits the tyrosine autophosphorylation of stem cell factor (SCF) receptor, c-kit, with IC50 of 0.1-1 μM, as well as ERK1/2 phosphorylation, a signaling event downstream of c-kit activation. It also inhibits SCF-induced proliferation of MO7E cells with IC50 of 0.29 μM, and induces apoptosis. [2]
in vivo Orantinib (SU6668) (75-200 mg/kg) induces tumor growth inhibition against a broad range of tumor types in xenograft models in athymic mice, including A375, Colo205, H460, Calu-6, C6, SF763T, and SKOV3TP5 cells. It (75 mg/kg) also suppresses tumor angiogenesis of C6 glioma xenografts. [1] In a tumor model of HT29 human colon carcinoma, this compound (200 mg/kg) decreases the average vessel permeability and average fractional plasma volume in the tumor rim and core. It promotes abnormal stromal development at the periphery of carcinomas. [3] In a rabbit VX2 liver tumor model, TSU-68 (200 mg/kg) augments the effect of chemotherapeutic infusion. [4]

プロトコル(参考用のみ)

キナーゼアッセイ trans-Phosphorylation Reactions
Tyrosine kinase assays to quantitate the trans-phosphorylation activity of Flk-1 and FGFR1 are performed in 96-well microtiter plates precoated (20 μg/well in PBS; incubated overnight at 4 °C) with the peptide substrate poly-Glu,Tyr (4:1). Excess protein binding sites are blocked with 1-5% (w/v) BSA in PBS. Purified GST-FGFR1 (kinase domain) or GST-Flk-1 (cytoplasmic domain) fusion proteins are then added to the microtiter wells in 2 × concentration kinase dilution buffer consisting of 100 mM HEPES, 50 mM NaCl, 40 μM NaVO4, and 0.02% (w/v) BSA. The final enzyme concentration for GST-Flk-1 and GST-FGFR1 is 50 ng/mL. Orantinib (SU6668) is dissolved in DMSO at 100× the final required concentration and diluted 1:25 in H2O. Twenty-five μL of diluted this compound are subsequently added to each reaction well. The kinase reaction is initiated by the addition of different concentrations of ATP in a solution of MnCl2 so that the final ATP concentrations spanned the Km for the enzyme, and the final concentration of MnCl2 is 10 mM. The plates are incubated for 5-15 min at room temperature before stopping the reaction with the addition of EDTA. The plates are then washed three times with TBST. Rabbit polyclonal antiphosphotyrosine antisera are added to the wells at a 1: 10000 dilution in TBST containing 0.5% (w/v) BSA, 0.025% (w/v) nonfat dry milk, and 100 μM NaVO4 and incubated for 1 hour at 37 °C. The plates are then washed three times with TBST, followed by the addition of goat anti-rabbit antisera conjugated with HRP. The plates are incubated for 1 hour at 37 °C and then washed three times with TBST. The amount of phosphotyrosine in each well is quantitated after the addition of 2,2
細胞アッセイ 細胞株 HUVECs, and NIH-3T3 cells overexpressing PDGFRβ or EGFR
濃度 0.03-10 μM , dissolved in DMSO as 10 mM stock solution
反応時間 1 hour (before ligand stimulation)
実験の流れ

Cells are seeded (3 × 105 cells/35-mm well) in DMEM containing 10% (v/v) FBS and grow to confluence and then quiesced in DMEM containing 0.1% serum for 2 hours before drug treatment. HUVECs (seeded at 2 × 106 cells/10-cm plate) are grown to confluence in endothelial cell growth media and then quiesced in endothelial cell basal media containing 0.5% FBS for 24 hours before drug treatment. All cell lines are incubated with Orantinib (SU6668) for 1 hour before ligand stimulation (100 ng/mL) for 10 min. Western blotting is perfor
動物実験 動物モデル Mouse (Female, BALB/c, nu/nu) xenograft models of A375, Colo205, H460, Calu-6, C6, SF763T, and SKOV3TP5 tumor cells
投薬量 75-200 mg/kg
投与方法 Via i.p. injection or oral gavage once daily.

参考

  • https://pubmed.ncbi.nlm.nih.gov/10945623/
  • https://pubmed.ncbi.nlm.nih.gov/11222388/
  • https://pubmed.ncbi.nlm.nih.gov/14760097/
  • https://pubmed.ncbi.nlm.nih.gov/21184227/

カスタマーフィードバック

Data from [Mol Cell Proteomics, 2012]

Data from [Mol Cell Proteomics, 2012]

Data from [Angiogenesis, 2012, 15, 569-80]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

SMYD5 is a novel epigenetic gatekeeper of the mild hypothermia response [ bioRxiv, 2023, 2023.05.11.540170] PubMed: 37333301
SMYD5 is a novel epigenetic gatekeeper of the mild hypothermia response [ bioRxiv, 2023, 2023.05.11.540170] PubMed: 37333301
Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei [ J Pers Med, 2022, 12(2)258] PubMed: 35207746
Establishment and characterization of NCC-UPS4-C1: a novel cell line of undifferentiated pleomorphic sarcoma from a patient with Li-Fraumeni syndrome [ Hum Cell, 2022, 10.1007/s13577-022-00671-y] PubMed: 35118583
Establishment and characterization of NCC-MFS4-C1: a novel patient-derived cell line of myxofibrosarcoma [ Hum Cell, 2021, 34(6):1911-1918] PubMed: 34383271
Establishment and characterization of the NCC-GCTB4-C1 cell line: a novel patient-derived cell line from giant cell tumor of bone [ Hum Cell, 2021, 10.1007/s13577-021-00639-4] PubMed: 34731453
Establishment and characterization of novel patient-derived cell lines from giant cell tumor of bone [ Hum Cell, 2021, 10.1007/s13577-021-00579-z] PubMed: 34304386
The Meningioma Enhancer Landscape Delineates Novel Subgroups and Drives Druggable Dependencies [ Cancer Discov, 2020, CD-20-0160] PubMed: 32703768
Establishment and characterization of NCC-MFS2-C1: a novel patient-derived cancer cell line of myxofibrosarcoma [ Hum Cell, 2020, 10.1007/s13577-020-00420-z] PubMed: 32870449
Multi-omic Profiling Reveals Dynamics of the Phased Progression of Pluripotency. [ Cell Syst, 2019, 8(5):427-445] PubMed: 31078527

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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