BLU-554 (Synonyms: BLU-554) |
カタログ番号GC19075
One-Click Copy Product Info
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BLU-554は線維芽細胞成長因子受容体4 (FGFR4)の選択性の阻害剤である(IC50 = 5nM)。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1707289-21-1
Sample solution is provided at 25 µL, 10mM.
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BLU-554は線維芽細胞成長因子受容体4 (FGFR4)の選択性の阻害剤である(IC50 = 5nM)[1]。BLU-554は、FGFR4キナーゼの活性を選択的に阻害し、FGF19-FGFR4経路を遮断し、よって腫瘍細胞の増殖と成長を阻害する[2]。BLU-554は、肝細胞癌の治療によく使われる[3-4]。
MKN-45細胞で、BLU-554 (0.05μM, 0.5μM, 5μM; 48h)は、胃癌細胞株MKN-45の増殖を阻害する[5]。HuH-7とJHH-7細胞で、BLU-554 (0-1250nM；12時間、48時間)は細胞でFGFR4活性を効果的に阻害できる[6]。PC9-4X細胞で、BLU-554 (1μM; 72h)はgefitinibのIC50を減らす[7]。
SW480-ELF4細胞皮下腫瘍マウスモデルで、BLU-554 (10mg/kg；胃内；9週間)とKX2-391の併用は、ELF4媒介のCRC転移を著しく阻害する[8]。Hepa1-6-ETV4異種移植マウスモデルで、BLU-554 (100mg/kg；胃内；9週間)の単独治療は、肺の転移を部分的に減らし、Hepa1-6-ETV4のOSを延ばした[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.
| 細胞実験[1]: | |
細胞株 | MKN-45細胞 |
準備方法 | 細胞を消化し、再懸濁し、計数し、5000細胞/ウェルの密度で播種した。接着後、細胞を前述通りに構成された2つの阻害剤溶液で48時間培養し、96ウェルのプレート(100μL/ウェル)の中の培地を交換した。BLU-554をジメチルスルホキシドと混合し、5mg/mLの母液を作製し、完全に溶解するまでボルテックスした。使用時に、溶液を完全培地と共に0.05, 0.5と5μMに希釈し、ボルテックスし混合し、保存した。 |
反応条件 | 0.05μM、0.5μM、5μM；48時間 |
アプリケーション | BLU-554は胃癌細胞株MKN-45の増殖を阻害する。 |
| 動物実験 [2]: | |
動物モデル | SW480-ELF4細胞皮下腫瘍マウスモデル |
準備方法 | 6週齢のBALB/cヌードマウスをランダムにグループに分け（10匹/グループ）、尾静脈または脾臓内注射転移モデルを建て、それぞれ1×10⁶または2×10⁶のルシフェラーゼ標識のCRC細胞を注射した。処理は接種の1週間後に始め、BLU-554 (10mg/kg)、KX2-391 (15mg/kg)または併用の薬剤を毎日経口投与し、溶媒対照群を設置した。D-ルシフェリンを毎週腹腔内注射し、IVISイメージングし、腫瘍の成長を記録した。マウスを9週間後に、肺と肝臓の転移、生存時間を評価した。 |
投与形態 | 10mg/kg；胃内；9週間 |
アプリケーション | BLU-554とKX2-391の併用は、ELF4-媒介のCRC転移を著しく阻害する。 |
References: | |
| Cas No. | 1707289-21-1 | SDF | |
| 同義語 | 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 | ||
| Formula | C24H24Cl2N4O4 | M.Wt | 503.38 |
| 溶解度 | DMSO : ≥ 25 mg/mL (49.66 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.9866 mL | 9.9329 mL | 19.8657 mL |
| 5 mM | 397.3 μL | 1.9866 mL | 3.9731 mL |
| 10 mM | 198.7 μL | 993.3 μL | 1.9866 mL |
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Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 17 reference(s) in Google Scholar.)