| 名稱 | Taselisib |
| 描述 | Taselisib (GDC-0032) is an orally bioavailable inhibitor of the class I phosphatidylinositol 3-kinase (PI3K) alpha isoform (PIK3CA), with potential antineoplastic activity. |
| 細胞實驗 | GDC-0032 is dissolved in DMSO. Cells are seeded in replicates of 6 in 96-well plates with 500 to 5,000 cells/well overnight and then treated with GDC-0032. After 4 days, the media are removed and the cells are fixed with 4% glutaraldehyde for 30 minutes. Fixed cells are stained with 0.1% crystal violet for 2 minutes, then washed, and dissolved in 10% acetic acid. |
| 激酶實驗 | Characterization of Biochemical and Cellular Activity in Vitro: Enzymatic activity of the class I PI3K isoforms is measured using a fluorescence polarization assay that monitors formation of the product 3,4,5-inositoltriphosphate molecule as it competes with fluorescently labeled PIP3 for binding to the GRP-1 pleckstrin homology domain protein. An increase in phosphatidyl inositide-3-phosphate product results in a decrease in fluorescence polarization signal as the labeled fluorophore is displaced from the GRP-1 protein binding site. Class I PI3K isoforms are expressed and purified as heterodimeric recombinant proteins. Tetramethylrhodamine-labeled PIP3 (TAMRA-PIP3), di-C8-PIP2, and PIP3 detection reagents are purchased from Echelon Biosciences. PI3Kα is assayed under initial rate conditions in the presence of 10 mM Tris (pH 7.5), 25 μM ATP, 9.75 μM PIP2, 5% glycerol, 4 mM MgCl2, 50 mM NaCl, 0.05% (v/v) Chaps, 1 mM dithiothreitol, and 2% (v/v) DMSO at 60 ng/mL. After assay for 30 min at 25 °C, reactions are terminated with a final concentration of 9 mM EDTA, 4.5 nM TAMRA-PIP3, and 4.2 μg/mL GRP-1 detector protein before reading fluorescence polarization on an Envision plate reader. IC50 values are calculated from the fit of the dose-response curves to a 4-parameter equation. Each reported value is an average of three experiments, and all have a standard deviation less than one geometric mean. |
| 體外活性 | GDC-0032與氟維司群聯(lián)用,增強氟維司群活性,導(dǎo)致腫瘤消退和腫瘤生長延遲（91％腫瘤生長抑制（TGI））.此外,GDC-0032與他莫昔芬聯(lián)用,增強他莫昔芬在體內(nèi)的效力,GDC-0032的腫瘤生長抑制率為102％.GDC-0032藥代動力學(xué)大約與劑量成比例并且與時間無關(guān),平均t1/2為40小時. |
| 體內(nèi)活性 | 臨床前期數(shù)據(jù)表明,GDC-0032具有增加PI3Kα同種型（PIK3CA）突變體和HER2擴增的癌細胞系的活性。GDC-0032抑制MCF7-neo/HER2 細胞增殖,IC50為2.5 nM。GDC-0032是I類PI3Kα,δ和γ同種型的口服生物可利用的,有效的和選擇性的抑制劑,相對于PI3Kα同種型,其對PI3Kβ同種型抑制率低30倍。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 40 mg/mL (86.86 mM), Heating is recommended.
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | RG7604 | inhibit | Taselisib | Inhibitor | GDC0032 | Phosphoinositide 3-kinase | GDC 0032 | RG 7604 | PI3K |
| 相關(guān)產(chǎn)品 | Cyclamic acid sodium | Urea | Benzenesulfonamide | Quercetin Dihydrate | Apilimod | pNNP | Tioxolone | Myricetin | Isoprenaline hydrochloride | Erucic acid | Orthanilamide | Hydrochlorothiazide |
| 相關(guān)庫 | 抑制劑庫 | 經(jīng)典已知活性庫 | 抗癌活性化合物庫 | 已知活性化合物庫 | 激酶抑制劑庫 | 抗衰老化合物庫 | 抗肺癌化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |