LGK-974
(Synonyms: 2',3-二甲基-N-[5-(2-吡嗪基)-2-吡啶基]-[2,4'-联吡啶]-5-乙酰胺,WNT974) 目录号 : GC12392
LGK-974是一种高效且特异的Porcupine（PORCN）抑制剂。
Cas No.:1243244-14-5
Sample solution is provided at 25 µL, 10mM.
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LGK-974 is a potent and specific inhibitor of Porcupine (PORCN)[1]. By inhibiting PORCN, LGK-974 effectively inhibits endogenous Wnt/β‑catenin signaling, which is critical in various biological processes, including cell proliferation, differentiation, and migration[2]. LGK-974 is commonly utilized in cancer research, particularly in the study of its potential to inhibit tumor growth[3] and modulate the tumor microenvironment[4].
LGK-974 can reduce Wnt-dependent AXIN2 mRNA levels in HN30 cells with an IC50 of 0.3nM[5]. In HepG2 cells, treatment with LGK-974 at 10µM for 6h can increase radiosensitivity by elevating reactive oxygen species (ROS) levels[6].
LGK-974 (3mg/kg, 7d, oral) treatment can attenuate the monocytic response and improves the healing process following myocardial infarction in Mice with induced ischemia/reperfusion (I/R) injury[7]. Repeated systemic injections of LGK-974 (2mg/kg, twice daily for 8d, i.p.) can prevent the development of chemotherapy-induced neuropathic pain CINP in rats[8].
References:
[1]. Morgan JT, Raghunathan VK, Chang YR, et al. Wnt inhibition induces persistent increases in intrinsic stiffness of human trabecular meshwork cells. Exp Eye Res. 2015 Mar;132:174-8. doi: 10.1016/j.exer.2015.01.025. Epub 2015 Jan 30. PMID: 25639201; PMCID: PMC4352377.
[2]. Zhang Y, Wang X. Targeting the Wnt/β-catenin signaling pathway in cancer. J Hematol Oncol. 2020 Dec 4;13(1):165. doi: 10.1186/s13045-020-00990-3. PMID: 33276800; PMCID: PMC7716495.
[3]. Guimaraes PPG, Tan M, Tammela T, et al. Potent in vivo lung cancer Wnt signaling inhibition via cyclodextrin-LGK974 inclusion complexes. J Control Release. 2018 Nov 28;290:75-87. doi: 10.1016/j.jconrel.2018.09.025. Epub 2018 Oct 2. PMID: 30290244; PMCID: PMC6441337.
[4]. Tang Y, Jiang M, Chen A, et al. Porcupine inhibitor LGK‑974 inhibits Wnt/β‑catenin signaling and modifies tumor‑associated macrophages resulting in inhibition of the malignant behaviors of non‑small cell lung cancer cells. Mol Med Rep. 2021 Aug;24(2):550. doi: 10.3892/mmr.2021.12189. Epub 2021 Jun 3. PMID: 34080032; PMCID: PMC8185506.
[5]. Liu J, Pan S, Hsieh MH, et al. Targeting Wnt-driven cancer through the inhibition of Porcupine by LGK974. Proc Natl Acad Sci U S A. 2013 Dec 10;110(50):20224-9. doi: 10.1073/pnas.1314239110. Epub 2013 Nov 25. PMID: 24277854; PMCID: PMC3864356.
[6]. Tian D, Shi Y, Chen D, et al. The Wnt inhibitor LGK-974 enhances radiosensitivity of HepG2 cells by modulating Nrf2 signaling. Int J Oncol. 2017 Aug;51(2):545-554. doi: 10.3892/ijo.2017.4042. Epub 2017 Jun 14. PMID: 28627706.
[7]. Meyer IS, Li X, Meyer C, et al. Blockade of Wnt Secretion Attenuates Myocardial Ischemia-Reperfusion Injury by Modulating the Inflammatory Response. Int J Mol Sci. 2022 Oct 14;23(20):12252. doi: 10.3390/ijms232012252. PMID: 36293109; PMCID: PMC9602582.
[8]. Kim HK, Bae J, Lee SH, et al. Blockers of Wnt3a, Wnt10a, or β-Catenin Prevent Chemotherapy-Induced Neuropathic Pain In Vivo. Neurotherapeutics. 2021 Jan;18(1):601-614. doi: 10.1007/s13311-020-00956-w. Epub 2020 Oct 30. PMID: 33128175; PMCID: PMC8116404.
LGK-974是一种高效且特异的Porcupine（PORCN）抑制剂[1]。通过抑制PORCN，LGK-974可以有效抑制内源性Wnt/β-连环蛋白信号通路，该信号通路在细胞增殖、分化和迁移等多种生物过程中起关键作用[2]。LGK-974常用于癌症研究，特别是在抑制肿瘤生长[3]和调节肿瘤微环境的潜力研究中[4]。
LGK-974可在HN30细胞中以0.3nM的IC50降低Wnt依赖的AXIN2 mRNA水平[5]。在HepG2细胞中，使用10µM的LGK974处理6小时可通过增加活性氧（ROS）水平提高放射敏感性[6]。
LGK-974（3mg/kg，7天，口服）治疗可减轻单核细胞反应，并改善小鼠在诱导缺血/再灌注（I/R）损伤后的心肌梗死愈合过程[7]。反复系统注射LGK-974（2mg/kg，每天两次，共8天，腹腔注射）可预防大鼠化疗诱导的神经病理性疼痛（CINP）[8]。
| Cell experiment [1]: | |
Cell lines | HepG2 |
Preparation Method | HepG2 cells were treated with 10µM LGK-974 and 4 Gy ionizing radiation for 6h. Then intracellular ROS levels were measured by fluorescence indicator 2,7-dichlorodi-hydrofluorescein diacetate (H2DCFH-DA). |
Reaction Conditions | 10µM, 6h |
Applications | LGK-974 treatment increases the radiosensitivity of HepG2 cells by increasing the level of ROS. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | Ischemia/reperfusion (I/R) injury was induced in female C57BL/6 mice aged 10–12 weeks and then were treated with LGK-974 (3mg/kg). Heart tissue samples from the infarct area were collected 2 days after induction of I/R injury, and single-cell suspensions were prepared for flow cytometry analysis. |
Dosage form | 3mg/kg, 7d, oral |
Applications | LGK-974 treatment reduced infiltration of leukocytes and myeloid response following I/R injury. |
References: | |
| Cas No. | 1243244-14-5 | SDF | |
| 别名 | 2',3-二甲基-N-[5-(2-吡嗪基)-2-吡啶基]-[2,4'-联吡啶]-5-乙酰胺,WNT974 | ||
| 化学名 | 2-[5-methyl-6-(2-methylpyridin-4-yl)pyridin-3-yl]-N-(5-pyrazin-2-ylpyridin-2-yl)acetamide | ||
| Canonical SMILES | CC1=C(N=CC(=C1)CC(=O)NC2=NC=C(C=C2)C3=NC=CN=C3)C4=CC(=NC=C4)C | ||
| 分子式 | C23H20N6O | 分子量 | 396.44 |
| 溶解度 | ≥ 19.8mg/mL in DMSO | 储存条件 | Store at -20° C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5224 mL | 12.6122 mL | 25.2245 mL |
| 5 mM | 0.5045 mL | 2.5224 mL | 5.0449 mL |
| 10 mM | 0.2522 mL | 1.2612 mL | 2.5224 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >99.50%
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