| 名稱 | Poziotinib |
| 描述 | Poziotinib (NOV120101)(NOV120101; HM781-36B) is an irreversible HER1/2/4 inhibitor (IC50s: 3/5/23 nM). |
| 細(xì)胞實(shí)驗(yàn) | Viable cell growth is determined by an MTT reduction assay. Briefly, all cell lines are seeded at a density of 3 × 103 per well in 96-well culture plates and then incubated at 37 °C for 24 h. The cells are then treated with 0.001, 0.01, 0.1, or 10 μM of HM781-36B. Three days later, 50 μg of MTT are added to each well and the samples are then incubated for 4 h to reduce the dye. Next, the samples are treated with DMSO, after which the absorbance of the converted dye in the living cells is measured at a wavelength of 540 nm. Six replicate wells are used for each analysis, and at least three independent experiments are conducted. Data points shown represent the mean while bars represent the SE.(Only for Reference) |
| 激酶實(shí)驗(yàn) | Enzyme activity assay: To determine the IC50 values of HM781-36B for kinase inhibition, enzymes of EGFR, HER2, and HER4 are expressed as recombinant proteins in Sf9 insect cells. Enzyme selectivity screening is then performed using a tyrosine kinase assay kit. Briefly, the reactions are performed in 96 well polystyrene round-bottomed plates containing kinase buffer composed of 100 mM HEPES (pH 7.4), 25 mM MgCl2, 10 mM MnCl2 and 250 μM Na3VO4. The reactions are initiated by the addition of 100 ng/assay enzyme, 100 μM ATP, and 10 ng/mL poly(Glu, Tyr). After 1 h of incubation at room temperature, the reactions are terminated by adding 6 mM EDTA solution and then anti-phosphotyrosine antibody, PTK Green Tracer, and FP dilution buffer mixtures. The fluorescence polarization values are then measured after 30 min at room temperature using a Victor3 microplate reader. Finally, the IC50 values were calculated using the following equation: Y = bottom + (top–bottom)/(1 + 10(X-logIC50)). |
| 體外活性 | 在負(fù)荷N87人胃癌異種移植物的裸鼠體內(nèi),Poziotinib（0.5 mg/kg,p.o.）可明顯抑制腫瘤生長,Poziotinib 與 5-FU聯(lián)用可更有效地抑制腫瘤生長. |
| 體內(nèi)活性 | Poziotinib對EGFR磷酸化和下游信號級聯(lián)放大的關(guān)鍵組分有抑制作用,如STAT3,AKT和ERK,且對HER2擴(kuò)增的胃癌細(xì)胞生長有特異性抑制效果。經(jīng)激活HER2擴(kuò)增的胃癌細(xì)胞中線粒體途徑,Poziotinib還可誘導(dǎo)G1細(xì)胞周期阻滯和細(xì)胞凋亡。此外,在HER2誘發(fā)的和HER2非擴(kuò)增的胃癌細(xì)胞中,Poziotinib與化療劑有協(xié)同效果。 |
| 存儲(chǔ)條件 | keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 91 mg/mL (185.2 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | Poziotinib | NOV-120101 | NOV 120101 |
| 相關(guān)產(chǎn)品 | Gefitinib | Metronidazole | 5-Fluorouracil | Stavudine | Tributyrin | Dextran sulfate sodium salt (MW 4500-5500) | Myricetin | Sorafenib | L-Ascorbic acid | Acetylcysteine | Sodium 4-phenylbutyrate | Kaempferol |
| 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 | 高選擇性抑制劑庫 | 膜蛋白靶向化合物庫 | 酪氨酸激酶分子庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |