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BLU-554 Sale

(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)。

BLU-554 Chemical Structure

Cas No.:1707289-21-1

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥969.00
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1mg
¥398.00
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5mg
¥875.00
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10mg
¥1,400.00
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25mg
¥2,380.00
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50mg
¥3,570.00
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Sample solution is provided at 25 µL, 10mM.

Description

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]

实验参考方法

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:
[1]. 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.
[2]. 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.

化学性质

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
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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
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