BLU-554 (Synonyms: BLU-554) |
Catalog No.GC19075
One-Click Copy Product Info
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BLU-554 is a selective inhibitor of fibroblast growth factor receptor 4 (FGFR4) (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 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.
| 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 | |
| Synonyms | 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 |
| Solubility | 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 | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 17 reference(s) in Google Scholar.)