Orantinib
作者：齊岳
發布時間：2023-08-25
09:00:26
點擊數：
產品名稱：Orantinib
產品描述：
| 產品描述 | TSU-68, a excellent effective against PDGFR autophosphorylation with Ki of 8 nM, also highly inhibits Flk-1 and FGFR1 trans-phosphorylation. It shows little effect against IGF-1R, Met, Src, Lck, Zap70, Abl and CDK2 and does not suppresses EGFR. |
| 靶點活性 | PDGFRβ:8 nM(Ki) |
| 體外活性 | 在HT29人類結腸癌腫瘤模型中,TSU-68（200 mg/kg）降低腫瘤邊緣的平均血管通透性和腫瘤中心的平均血漿容積分數.在攜帶多種移植瘤的無胸腺小鼠,包括A375,Colo205,H460,Calu-6,C6,SF763T,和SKOV3TP5細胞等,TSU-68（75-200 mg/kg）抑制細胞生長.兔VX2肝臟腫瘤模型中, TSU-68（200 mg/kg）增加注射化學治療的效果.在C6神經膠細胞移植瘤中, TSU-68（75 mg/kg）也阻斷腫瘤血管生成. |
| 體內活性 | TSU-68是ATP競爭性抑制劑, 作用于Flk-1/KDR磷酸轉移, FGFR1磷酸轉移,和PDGFRβ激酶時, Ki分別為2.1 μM, 1.2 μM,和8 nM。在人類骨髓性白血病MO7E細胞中,TSU-68（IC50=0.1-1 μM）抑制肝細胞因子受體c-kit的酪氨酸自磷酸化, 也抑制ERK1/2磷酸化。在SCF刺激的MO7E細胞中,TSU-68（IC50=0.29 μM）也抑制細胞增殖,并誘導凋亡。過量表達PDGFRβ的NIH-3T3細胞中,TSU-68（0.03-0.1 μM）抑制PDGF刺激的PDGFRβ 酪氨酸磷酸化。在血管內皮生長因子刺激的HUVECs中,TSU-68（0.03-10 μM)抑制KDR酪氨酸磷酸化。在過量表達EGFR 的NIH-3T3細胞中, TSU-68(100 μM) 不抑制EGF刺激的EGFR酪氨酸磷酸化。TSU-68抑制血管內皮生長因子驅動的和FGF驅動的HUVECs分裂,平均IC50分別為0.34和 9.6 μM。 |
| 激酶實驗 | 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. SU6668 is dissolved in DMSO at 100× the final required concentration and diluted 1:25 in Water. Twenty-five μL of diluted SU6668 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 |
| 細胞實驗 | 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 SU6668 for 1 hour before ligand stimulation (100 ng/mL) for 10 min. Western blotting is perfor (Only for Reference) |
| 別名 | NSC 702827, SU6668, TSU-68 |
| 分子量 | 310.353 |
| 分子式 | C18H18N2O3 |
| CAS No. | 252916-29-3 |
存儲
Powder: -20°C for 3 years | In solvent: -80°C for 2 years
溶解度
1eq. NaOH: 31 mg/mL (100 mM)
DMSO: 31 mg/mL (100 mM)
( < 1 mg/mL refers to the product slightly soluble or insoluble )
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西安齊岳生物科技有限公司是集化學科研和定制與一體的高科技化學公司。業務范圍包括化學試劑和產品的研發、生產、銷售等。涉及產品為通用試劑的分銷、非通用試劑的定制與研發，涵蓋生物科技、化學品、中間體和化工材料等領域。
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