| 名稱 | PD158780 |
| 描述 | PD 158780 reversibly inhibits auto and transphosphorylation of all four members of the ErbB receptor superfamily: EGFR, ErbB2, ErbB3, and ErbB4 (IC50s: 8μM, 49 nM, 52 nM, and 52 nM in cell assay). |
| 細(xì)胞實(shí)驗(yàn) | All cell lines were maintained as monolayers in dMEM/F12, 50:50 containing 10% fetal bovine serum. For growth inhibition assays, dilutions of the designated compound in 10 μL were placed in 24-well Linbro plates (1.7 x 1.6 cm, flat bottom) followed by the addition of cells (2 × 10^4) in 2 mL of medium. The plates were incubated for 72 hr at 37 °C in a humidified atmosphere containing 5% CO 2 in air. Cell growth was determined by counting cells with a Coulter model AM electronic cell counter. For clone formation in soft agar, cells were trypsinized, and 10,000 cells/mL were seeded into DMEM/F12 medium containing 10% fetal bovine serum, 0.4% agarose, and the designated concentration of compound. One milliliter of this solution was placed over a bottom layer of the same medium containing 0.8% agarose in a 35-mm Petri dish and incubated at 37 °C in a humidified atmosphere containing 5% CO 2 in air. After 3 weeks, colonies were stained with p-iodonitrotetrazolium violet (INT) and quantitated with an image analyzer using the software NIH Image version 1.55. Incorporation of radiolabeled thymidine into cellular DNA was monitored by exposing compound-treated or control cells to [methyl)H]thymidine at a concentration of 1 μM and specific activity of 1 μCi/nmol. After 2 hr the cells were trypsinized and injected into 2 mL of ice-cold 15% trichloroacetic acid (TCA). The resulting precipitate was collected on glass fiber filters, washed five times with 2-mL aliquots of ice-cold 15% TCA, dried, and placed in scintillation vials plus 10 mL Ready gel [1]. |
| 激酶實(shí)驗(yàn) | Epidermal growth factor receptor was prepared from human A431 carcinoma cell shed membrane vesicles by immunoaffinity chromatography as previously described, and the assays were carried out as reported previously. The substrate used was based on a portion of phospholipase Cγ1, having the sequence Lys-His-Lys-Lys-LeuAla-Glu-Gly-Ser-Ala-Tyr472-Glu-Glu-Val. The reaction was allowed to proceed for 10 min at room temperature and then was stopped by the addition of 2 mL of 75 mM phosphoric acid. The solution was then passed through a 2.5 cm phosphocellulose disk which bound the peptide. This filter was washed with 75 mM phosphoric acid (5×), and the incorporated label was assessed by scintillation counting in an aqueous fluor. Control activity (no drug) gave a count of approximately 100 000 cpm. At least two independent dose-response curves were done and the IC50 values computed. The reported values are averages; variation was generally ±15% [1]. |
| 體外活性 | PD158780在A431人類表皮樣癌細(xì)胞中抑制了EGF受體的自磷酸化作用，IC50值為13 nM。PD158780對EGF受體具有很高的特異性，在Swiss 3T3成纖維細(xì)胞中，以低納摩爾濃度抑制了依賴EGF的受體自磷酸化和胸腺嘧啶的摻入。PD158780還抑制了SK-BR-3和MDA-MB-453乳腺癌細(xì)胞中由heregulin刺激的磷酸化作用，IC50值分別為49 nM和52 nM [1]。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | 10% DMSO+40% PEG300+5% Tween 80+45% Saline : 3.57 mg/mL (10.81 mM), Solution.
10% DMSO+90% Saline : < 3.57 mg/mL (10.81 mM), Lower concentrations may be soluble, but exact solubility limit is unknown.
Ethanol : 8 mg/mL (24.23 mM), Sonication is recommended.
DMSO : 35.71 mg/mL (108.15 mM), Sonication is recommended.
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| 關(guān)鍵字 | PD-158780 | PD158780 | PD 158780 | Inhibitor | inhibit | HER1 | ErbB4 | ErbB3 | ErbB2 | ErbB-1 | Epidermal growth factor receptor | EGFR |
| 相關(guān)產(chǎn)品 | Neratinib | Lapatinib | Chalcone | Gefitinib | Erlotinib | Osimertinib | Erlotinib hydrochloride | Afatinib | Afatinib Dimaleate | Lidocaine Hydrochloride hydrate | Khellin | Brigatinib |
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