| 名稱 | Orantinib |
| 描述 | Orantinib (NSC 702827) , 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. |
| 細(xì)胞實(shí)驗(yàn) | 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) |
| 激酶實(shí)驗(yàn) | 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 |
| 體外活性 | 在HT29人類結(jié)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?jǐn)?shù).在攜帶多種移植瘤的無(wú)胸腺小鼠,包括A375,Colo205,H460,Calu-6,C6,SF763T,和SKOV3TP5細(xì)胞等,TSU-68（75-200 mg/kg）抑制細(xì)胞生長(zhǎng).兔VX2肝臟腫瘤模型中, TSU-68（200 mg/kg）增加注射化學(xué)治療的效果.在C6神經(jīng)膠細(xì)胞移植瘤中, TSU-68（75 mg/kg）也阻斷腫瘤血管生成. |
| 體內(nèi)活性 | TSU-68是ATP競(jìng)爭(zhēng)性抑制劑, 作用于Flk-1/KDR磷酸轉(zhuǎn)移, FGFR1磷酸轉(zhuǎn)移,和PDGFRβ激酶時(shí), Ki分別為2.1 μM, 1.2 μM,和8 nM。在人類骨髓性白血病MO7E細(xì)胞中,TSU-68（IC50=0.1-1 μM）抑制肝細(xì)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(xì)胞中,TSU-68（IC50=0.29 μM）也抑制細(xì)胞增殖,并誘導(dǎo)凋亡。過(guò)量表達(dá)PDGFRβ的NIH-3T3細(xì)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(nèi)皮生長(zhǎng)因子刺激的HUVECs中,TSU-68（0.03-10 μM)抑制KDR酪氨酸磷酸化。在過(guò)量表達(dá)EGFR 的NIH-3T3細(xì)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(nèi)皮生長(zhǎng)因子驅(qū)動(dòng)的和FGF驅(qū)動(dòng)的HUVECs分裂,平均IC50分別為0.34和 9.6 μM。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | 1eq. NaOH : 31 mg/mL (100 mM)
DMSO : 40 mg/mL (128.89 mM), Sonication is recommended.
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| 關(guān)鍵字 | FGFR | inhibit | TSU68 | Platelet-derived growth factor receptor | NSC-702827 | TSU 68 | Orantinib | Vascular endothelial growth factor receptor | VEGFR | Apoptosis | Inhibitor | SU-6668 | NSC702827 | PDGFR | SU 6668 | Fibroblast growth factor receptor |
| 相關(guān)產(chǎn)品 | L-Glutamic acid | Metronidazole | Ferulic Acid | 5-Fluorouracil | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Tributyrin | Myricetin | L-Ascorbic acid | Acetylcysteine | Salicylic acid | Sodium 4-phenylbutyrate |
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