| 名稱 | CH5132799 |
| 描述 | CH5132799 has been used in trials studying the treatment of Solid Tumors. |
| 細(xì)胞實(shí)驗(yàn) | The cell lines are added to the wells of 96-well plates containing 0.076 to 10,000 nM CH5132799 and incubated at 37 °C. After 4 days of incubation, Cell Counting Kit-8 solution is added and, after incubation for several more hours, absorbance at 450 nm is measured with Microplate-Reader iMark. The antiproliferative activity is calculated by the formula (1- T/C) × 100 (%), in which T and C represent absorbance at 450 nm of the cells treated with CH5132799 (T) and that of untreated control cells (C). The IC50 values are calculated by using Microsoft Excel 2007. (Only for Reference) |
| 激酶實(shí)驗(yàn) | PI3K Assay: The E542K, E545K, and H1047R mutants of PI3Kα are prepared with an overlapped extension-polymerase chain reaction. Glutathione S-transferase-tagged PI3Kα mutants and His-tagged p85α are co-expressed with BAC-TO-BAC Baculovirus Expression System. The inhibitory activities of CH5132799 on PI3Kα (p110α/p85α), PI3Kβ(p110β/p85α), PI3Kδ (p110δ/p85α), PI3Kγ (p110γ), PI3KC2α, PI3KC2β, Vps34, and PI3Kα mutants are determined by Adapta Universal Kinase Assay Kit. Time-resolved fluorescence is measured with an EnVision HTS microplate reader. IC50 values are calculated using XLfit. |
| 體外活性 | CH5132799作為臨床備用藥,表現(xiàn)出良好的口服生物利用度(小鼠中101%) 人肝微粒體穩(wěn)定性和體內(nèi)抗腫瘤活性.CH5132799在小鼠,大鼠,猴子和狗體內(nèi),表現(xiàn)出良好的口服生物利用度(F: 54.2-101%).在人乳腺癌(KPL-4: PI3Ka H1047R)異種移植小鼠模型中,用CH5132799（12.5 mg/kg,q.d.）口服治療顯示強(qiáng)烈的腫瘤消退.CH5132799在幾種不同的負(fù)荷PIK3CA突變型的異種移植模型中,表現(xiàn)出有效的體內(nèi)抗腫瘤活性.CH5132799在幾種具有PIK3CA突變的異種移植模型中顯示出強(qiáng)效的體內(nèi)抗腫瘤活性. |
| 體內(nèi)活性 | CH5132799處理PIK3CA突變的乳腺癌KPL-4細(xì)胞,磷酸化Akt及其直接底物和PRAS40和FoxO1/3a和磷酸化下游因子（包括S6K,S6和4E-BP1）,都被有效抑制。PIK3CA突變型的癌細(xì)胞系明顯對CH5132799敏感。在通過突變活化PI3K途徑的人腫瘤細(xì)胞系中,CH5132799顯示有效的抗增殖活性。CH5132799有效抑制KPL-4細(xì)胞中的AKT磷酸化。CH5132799選擇性抑制I類PI3Ks,PI3Kα：IC50 = 0.014 μM,PI3Kβ：IC50 = 0.12 μM,PI3Kδ：IC50 = 0.50 μM,PI3Kγ：IC50 = 0.036 μM,但是對II類PI3Ks,III類PI3k和mTOR的抑制作用較弱,對26種蛋白激酶也沒有抑制活性（IC50 > 10 μM）。與野生型PI3Kα相比,CH5132799對致癌基因突變體E542K（IC50 = 6.7 nM）,E545K（IC50 = 6.7 nM）和H1047R（IC50 = 5.6 nM）顯示出更強(qiáng)的針對PI3Kα的抑制活性。 |
| 存儲條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 1 mg/ml, Sonication is recommended.
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| 關(guān)鍵字 | Phosphoinositide 3-kinase | Inhibitor | CH-5132799 | CH5132799 | PI3K | CH 5132799 | inhibit |
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| 相關(guān)庫 | 抑制劑庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | ReFRAME 相關(guān)化合物庫 | 激酶抑制劑庫 | 抗衰老化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |