BLU-554
(Synonyms: BLU-554) 目录号 : GC19075
BLU-554是成纤维细胞生长因子受体4（FGFR4）的选择性抑制剂（IC50 = 5nM）。
Cas No.:1707289-21-1
Sample solution is provided at 25 µL, 10mM.
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BLU-554 is a selective inhibitor of fibroblast growth factor receptor 4 (FGFR4) (IC50 = 5nM) [1]. BLU-554 selectively inhibits the activity of FGFR4 kinase, blocking the FGF19-FGFR4 pathway, thereby inhibiting the proliferation and growth of tumor cells [2]. BLU-554 is commonly used to treat hepatocellular carcinoma [3-4].
In MKN-45 cells, BLU-554 (0.05μM, 0.5μM, 5μM; 48h) inhibit the proliferation of gastric cancer cell line MKN-45 [5]. In HuH-7 and JHH-7 cells, BLU-554 (0-1250nM; 12h, 48h) can effectively inhibit FGFR4 activity in cells [6]. in PC9-4X cells, BLU-554 (1μM; 72h) reduces the IC50 of gefitinib [7].
In SW480-ELF4 cells subcutaneous tumor mice model, combination of BLU-554 (10mg/kg; ig; 9 weeks) and KX2-391 significantly inhibits ELF4-mediated CRC metastasis [8]. In Hepa1-6-ETV4 xenograft mice models, BLU-554 (100mg/kg; ig; 9 weeks) monotherapy partially reduced lung metastasis and lengthened the OS of the Hepa1-6-ETV4 [9].
References:
[1]. Dogan-Topal B, Li W, Schinkel AH, et al. Quantification of FGFR4 inhibitor BLU-554 in mouse plasma and tissue homogenates using liquid chromatography-tandem mass spectrometry. Journal of Chromatography B. 2019 Mar 15; 1110: 116-123.
[2]. Subbiah V, Pal SK. Precision oncology for hepatocellular cancer: Slivering the liver by FGF19–FGFR4–KLB pathway inhibition. Cancer discovery. 2019 Dec 1; 9(12): 1646-1649.
[3]. Kim RD, Sarker D, Meyer T, et al. First-in-human phase I study of fisogatinib (BLU-554) validates aberrant fibroblast growth factor 19 signaling as a driver event in hepatocellular carcinoma. Cancer Discovery. 2019; 9(12): 1696-1707.
[4]. Kim R, Sarker D, Macarulla T, et al. Phase 1 safety and clinical activity of BLU-554 in advanced hepatocellular carcinoma (HCC). Annals of Oncology. 2017 Sep 1; 28: v122.
[5]. Zhang X, Zhang X, Han R, et al. BLU-554, a selective inhibitor of FGFR4, exhibits anti-tumour activity against gastric cancer in vitro. Biochemical and Biophysical Research Communications. 2022 Mar 5; 595: 22-27.
[6]. Tao Z, Cui Y, Xu X, et al. FGFR redundancy limits the efficacy of FGFR4-selective inhibitors in hepatocellular carcinoma. Proceedings of the National Academy of Sciences. 2022 Oct 4; 119(40): e2208844119.
[7]. Liu D, Liu H, Gan J, et al. LY2874455 and abemaciclib reverse FGF3/4/19/CCND1 amplification mediated gefitinib resistance in NSCLC. Frontiers in Pharmacology. 2022 Jun 23; 13: 918317.
[8]. Chen X, Chen J, Feng W, et al. FGF19-mediated ELF4 overexpression promotes colorectal cancer metastasis through transactivating FGFR4 and SRC. Theranostics. 2023 Feb 22; 13(4): 1401.
[9]. Xie M, Lin Z, Ji X, et al. FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2. Journal of Hepatology. 2023 Jul 1; 79(1): 109-125.
BLU-554是成纤维细胞生长因子受体4（FGFR4）的选择性抑制剂（IC50 = 5nM） [1]。BLU-554选择性抑制FGFR4激酶活性，阻断FGF19-FGFR4通路，从而抑制肿瘤细胞的增殖和生长 [2]。BLU-554常用于治疗肝细胞癌 [3-4]。
在MKN-45细胞中，BLU-554（0.05μM，0.5μM，5μM；48h）可抑制胃癌细胞系MKN-45的增殖 [5]。在HuH-7和JHH-7细胞中，BLU-554（0-1250nM；12h，48h）可有效抑制细胞中的FGFR4活性 [6]。在PC9-4X细胞中，BLU-554（1μM；72h）降低gefitinib的IC50 [7]。
在SW480-ELF4细胞皮下肿瘤小鼠模型中，BLU-554（10mg/kg；ig；9周）联合KX2-391显著抑制ELF4介导的CRC转移 [8]。在Hepa1-6-ETV4异种移植小鼠模型中，BLU-554（100mg/kg；ig；9周）单药治疗可部分降低肺转移，并延长Hepa1-6-ETV4小鼠的OS [9]。
| Cell experiment [1]: | |
Cell lines | MKN-45 cells |
Preparation Method | The cells were digested, resuspended, counted, and plated at a density of 5000 cells/well. After adherence, cells were incubated with the two inhibitor solutions configured as previously mentioned for 48h, and media in the 96-well plate (100μL/well) was replaced. BLU-554 was mixed with dimethyl sulfoxide to make a 5mg/mL mother liquor, vortexed until completely dissolved. The solution was diluted with complete medium to 0.05, 0.5, and 5μM when used, vortexed to mix, and stored. |
Reaction Conditions | 0.05μM, 0.5μM, 5μM; 48h |
Applications | BLU-554 inhibit the proliferation of gastric cancer cell line MKN-45. |
| Animal experiment [2]: | |
Animal models | SW480-ELF4 cells subcutaneous tumor mice model |
Preparation Method | Six-week-old BALB/c nude mice were randomly divided into groups (10 mice per group) to establish a tail vein or intrasplenic injection metastasis model, and 1×10⁶ or 2×10⁶ luciferase-labeled CRC cells were injected, respectively. Treatment began 1 week after inoculation, and BLU-554 (10mg/kg), KX2-391 (15mg/kg) or combined drugs were given by gavage daily, and a vehicle control group was set up. D-luciferin was injected intraperitoneally every week for IVIS imaging to record tumor progression. Mice were killed after 9 weeks to evaluate lung and liver metastasis and survival time. |
Dosage form | 10mg/kg; ig; 9 weeks |
Applications | Combination of BLU-554 and KX2-391 significantly inhibits ELF4-mediated CRC metastasis. |
References: | |
| Cas No. | 1707289-21-1 | SDF | |
| 别名 | BLU-554 | ||
| Canonical SMILES | C=CC(N[C@@H]1[C@H](NC2=NC=C3C=C(C4=C(Cl)C(OC)=CC(OC)=C4Cl)C=CC3=N2)COCC1)=O | ||
| 分子式 | C24H24Cl2N4O4 | 分子量 | 503.38 |
| 溶解度 | DMSO : ≥ 25 mg/mL (49.66 mM) | 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 | 1.9866 mL | 9.9329 mL | 19.8657 mL |
| 5 mM | 0.3973 mL | 1.9866 mL | 3.9731 mL |
| 10 mM | 0.1987 mL | 0.9933 mL | 1.9866 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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