LGK-974

製品コードS7143 バッチS714306

印刷

化学情報

Chemical Structure Synonyms NVP-LGK974, WNT974 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C23H20N6O
分子量 396.44 CAS No. 1243244-14-5
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 79 mg/mL (199.27 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Clear solution
5%DMSO Corn oil
1.35mg/ml Taking the 1 mL working solution as an example, add 50 μL of 27 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 LGK-974 (NVP-LGK974, WNT974) is a potent and specific PORCN inhibitor, and inhibits Wnt signaling with IC50 of 0.4 nM in TM3 cells. Phase 1.
in vitro LGK974 effectively displaces [3H]-GNF-1331 with IC50 of 1 nM in the PORCN radioligand binding assay, and shows no major cytotoxicity in cells up to 20 µM. LGK974 shows comparable inhibitory activities against all tested Wnts with IC50 ranging from 0.05 to 2.4 nM, which is consistent with the genetic loss of PORCN phenotype. [1] LGK974 specifically inhibits the growth of three RNF43-mutant cell lines, HPAF-II, PaTu 8988S, and Capan-2. [2]
in vivo In a murine MMTV-Wnt1 tumor model and a human head and neck squamous cell carcinoma model (HN30), LGK974 (3 mg/kg) inhibits Wnt signaling in vivo and induces tumor regression without significant body weight loss in the mice. [1] LGK974 (5 mg/kg, p.o., BID) also inhibits tumor growth of RNF43-mutant pancreatic tumors (HPAF-II and Capan-2) in vivo. [2]
特徴 Orally bioavailable Porcupine-specific inhibitor that has been tested in Phase I clinical trials for treatment of malignancies dependent on Wnt ligands.

プロトコル(参考用のみ)

細胞アッセイ 細胞株 HPAF-II, PaTu 8988S, and Capan-2 cells
濃度 ~1 μM
反応時間 3 days
実験の流れ

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 humidified atmosphere containing 5% CO2. Cells are fixed with final 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.
動物実験 動物モデル A murine MMTV-Wnt1 tumor model and a human head and neck squamous cell carcinoma model (HN30)
投薬量 ~3 mg/kg daily
投与方法 Oral gavage

カスタマーフィードバック

Data from [Data independently produced by Breast Cancer Res, 2014, 16(4), 408]

Data from [Data independently produced by , , Nat Commun, 2017, 8:15945]

Data from [Data independently produced by , , J Clin Endocrinol Metab, 2015, 100(6): E836-44]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Integrated clinical and genomic analysis identifies driver events and molecular evolution of colitis-associated cancers [ Nat Commun, 2023, 14(1):110] PubMed: 36611031
Sema3C signaling is an alternative activator of the canonical WNT pathway in glioblastoma [ Nat Commun, 2023, 14(1):2262] PubMed: 37080989
WNT signaling in the tumor microenvironment promotes immunosuppression in murine pancreatic cancer [ J Exp Med, 2023, 220(1)e20220503] PubMed: 36239683
The CUT&RUN suspect list of problematic regions of the genome [ Genome Biol, 2023, 24(1):185] PubMed: 37563719
Single-cell RNA sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the Wnt3/β-catenin pathway in irradiated mice [ Redox Biol, 2023, 10.1016/j.redox.2023.102942] PubMed: 37918127
Single-cell RNA sequencing of intestinal crypts reveals vital events in damage repair and the double-edged sword effect of the Wnt3/β-catenin pathway in irradiated mice [ Redox Biol, 2023, 68:102942.] PubMed: 37918127
Rapid mechanosensitive migration and dispersal of newly divided mesenchymal cells aid their recruitment into dermal condensates [ PLoS Biol, 2023, 21(9):e3002316] PubMed: 37747910
Intravital imaging of Wnt/β-catenin and ATF2-dependent signalling pathways during tumour cell invasion and metastasis [ J Cell Sci, 2023, 136(3)jcs260285] PubMed: 36621522
Single-cell response to Wnt signaling activation reveals uncoupling of Wnt target gene expression [ Exp Cell Res, 2023, 429(2):113646] PubMed: 37271249
S1PR1 attenuates pulmonary fibrosis by inhibiting EndMT and improving endothelial barrier function [ Pulm Pharmacol Ther, 2023, S1094-5539(23)00040-8] PubMed: 37295666

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。