| 名稱 | LGK974 |
| 描述 | LGK974 (NVP-LGK974) is an effective and selective PORCN inhibitor and inhibits Wnt signaling (IC50: 0.4 nM) in TM3 cells. It has been used in trials studying the treatment of Metastatic Colorectal Cancer and Squamous Cell Carcinoma, Head And Neck. |
| 細(xì)胞實(shí)驗(yàn) | Cells are plated in growth medium in a 96-well plate at a density of 6,000–12,000 cells per well and treated with DMSO or 1 μM LGK974. After 3 d, the cells are treated with fresh growth medium containing 20 μM EdU, which is included in the Click-iT EdU Alexa Fluor 488 HCS assay kit, and the plate was incubated for 2 h at 37 °C in a humidi?ed atmosphere containing 5% CO2. Cells are ?xed with ?nal 4% (mass/vol) paraformaldehyde for 30 min, washed with PBS, permeabilized, and stained with 50 μg/mL Hoechst in PBS for 30 min. After wash, the cells are proceeded to EdU detection according to the instruction of Click-iT EdU assay kit. Triplet wells are performed for each condition. (Only for Reference) |
| 激酶實(shí)驗(yàn) | Radioligand binding assay: using the aforementioned membrane preps, filtration binding assays are performed. To reduce nonspecific binding, 96-well filtration plates are precoated as suggested by the manufacturer with 0.1% BSA and then washed four times with 0.1% BSA. Membrane preps (50 μg total protein) are incubated in polypropylene 96-well plates with 6.6 nM 3H-GNF-1331 in the presence or absence of a testing compound in binding buffer (50 mM Tris, pH 7.5, 5 mM MgCl2, 1 mM EDTA, 0.1% BSA) plus EDTA-free protease inhibitor mixture in a final volume of 150 μL for 3 h at room temperature. Binding reaction mixtures are then transferred to the precoated 96-well filtration plates, filtered, and washed using a 96-pin FilterMate Harvester. Radioactive signals are obtained using a Microplate Scintillation Counter TopCount. Curve fitting is performed using Prism[1]. |
| 體外活性 | 在小鼠MMTV-WNT1腫瘤模型和人的頭、頸部鱗狀細(xì)胞癌模型（hn30）中,LGK-974（3 mg/kg）對(duì)Wnt信號(hào)通路有抑制作用,其可誘導(dǎo)腫瘤退化且不影響小鼠體重.LGK-974（5 mg/kg,2次/天,p.o.）還可抑制RNF43-突變胰腺腫瘤(HPAF-II 和Capan-2)的生長(zhǎng) |
| 體內(nèi)活性 | LGK-974對(duì)測(cè)試的Wnts均有抑制作用（IC50：0.05-2.4 nM）。 在PORCN放射配體結(jié)合測(cè)定中,LGK-974可有效取代[3H]GNF -1331（IC50：1 nM）,且20 μM時(shí)細(xì)胞毒性也較小。LGK-974可特異抑制RNF43突變細(xì)胞株HPAF-II、PaTu 8988S和 Capan-2的生長(zhǎng)。 |
| 存儲(chǔ)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 | DMSO : 16.96 mg/mL (42.78 mM), Sonication is recommended.
10% DMSO+90% Corn Oil : 3.3 mg/mL (8.32 mM), Sonication is recommended.
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
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| 關(guān)鍵字 | WNT-974 | WNT 974 | Porcn | NVP-LGK-974 | NVP-LGK 974 | LGK974 |
| 相關(guān)產(chǎn)品 | IWP 12 | ETC-159 | GNF-1331 | Wnt-C59 | IWP-2 | WHN-88 | IWP L6 | GNF-6231 | Porcn-IN-1 | IWP-O1 | Zamaporvint |
| 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 | 抗結(jié)直腸癌化合物庫 | 抗感染化合物庫 | NO PAINS 化合物庫 | 抗病毒庫 | 臨床期小分子藥物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |