LGK974 (WNT974)

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）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
5%DMSO Corn oil

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 1.350mg/ml (3.41mM) 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 In the PORCN radioligand binding assay, LGK974 (WNT974) effectively displaces [3H]-GNF-1331 with an IC50 of 1 nM and shows no major cytotoxicity in cells up to 20 µM. It 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] This compound 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 (WNT974) (3 mg/kg) inhibits Wnt signaling in vivo and induces tumor regression without significant body weight loss in the mice. [1] This compound (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 (WNT974). 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

参考

  • https://pubmed.ncbi.nlm.nih.gov/24277854/
  • https://pubmed.ncbi.nlm.nih.gov/23847203/

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：

CD36 enrichment in HER2-positive mesenchymal stem cells drives therapy refractoriness in breast cancer [ J Exp Clin Cancer Res, 2025, 44(1):19] PubMed: 39833955
Wnt signaling activation induces CTCF binding and loop formation at cis-regulatory elements of target genes [ Genome Res, 2025, 10.1101/gr.279684.124] PubMed: 40550689
Developmental signals control chromosome segregation fidelity during pluripotency and neurogenesis by modulating replicative stress [ Nat Commun, 2024, 15(1):7404] PubMed: 39191776
Loss of ARID3A perturbs intestinal epithelial proliferation-differentiation ratio and regeneration [ J Exp Med, 2024, 221(10)e20232279] PubMed: 39150450
Physiological regulation of neuronal Wnt activity is essential for TDP-43 localization and function [ EMBO J, 2024, 43(16):3388-3413] PubMed: 38918634
GPA33 expression in colorectal cancer can be induced by WNT inhibition and targeted by cellular therapy [ Oncogene, 2024, ] PubMed: 39472498
Unbalancing cAMP and Ras/MAPK pathways as a therapeutic strategy for cutaneous neurofibromas [ JCI Insight, 2024, 9(3)e168826] PubMed: 38175707
Higher overall survival rates of oral squamous cell carcinoma treated with metronomic neoadjuvant chemotherapy [ Am J Cancer Res, 2024, 14(3):1033-1051] PubMed: 38590400
Porcupine inhibitors LGK-974 and ETC-159 inhibit Wnt/β-catenin signaling and result in inhibition of the fibrosis [ Toxicol In Vitro, 2024, 104:105986] PubMed: 39647516
The developmental basis of fingerprint pattern formation and variation [ Cell, 2023, 186(5):940-956.e20] PubMed: 36764291

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。