FGFR4
FGFR4 is a receptor tyrosine kinase within the FGFR1-4 family, and normal adult tissues show differential FGFR expression patterns that support receptor-specific functional diversity[1]. Mechanistically, βKlotho (KLB) combines with selected FGFR isoforms to determine endocrine FGF19/FGF21 metabolic activity, while FGF19 requires KLB for FGFR4 binding, intracellular signaling, and downstream gene modulation[2][3]. In hepatocyte models, bile acid-activated FXR induces FGF19, and the hepatic FGF19-FGFR4-ERK1/2 pathway inhibits CYP7A1 expression, linking FGFR4 to bile acid synthesis control[4]. In mouse models, FGFR4 activation mediates FGF19-induced hepatocyte proliferation and suppression of bile acid biosynthesis, but it is not essential for FGF19 effects on glucose and lipid metabolism[5]. Compared with related isoforms, FGF19 shows unique specificity for FGFR4, and this ligand-receptor selectivity distinguishes FGFR4-centered signaling from broader FGFR1-3 biology[6]. For experimental applications, fisogatinib/BLU-554 and BLU9931 provide selective FGFR4 inhibition tools for studying FGF19-driven hepatocellular carcinoma models and activated FGFR4 signaling[7][8].
References:
- [1]. Hughes SE. Differential expression of the fibroblast growth factor receptor (FGFR) multigene family in normal human adult tissues. J Histochem Cytochem. 1997 Jul;45(7):1005-19. doi: 10.1177/002215549704500710. PMID: 9212826. et al. Differential expression of the fibroblast growth factor receptor (FGFR) multigene family in normal human adult tissues. J Histochem Cytochem. 1997 Jul;45(7):1005-19. [Content Brief]
- [2]. Kurosu H, et al. Tissue-specific expression of betaKlotho and fibroblast growth factor (FGF) receptor isoforms determines metabolic activity of FGF19 and FGF21. J Biol Chem. 2007 Sep 14;282(37):26687-26695. [Content Brief]
- [3]. Lin BC, et al. Liver-specific activities of FGF19 require Klotho beta. J Biol Chem. 2007 Sep 14;282(37):27277-27284. [Content Brief]
- [4]. Song KH, et al. Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression. Hepatology. 2009 Jan;49(1):297-305. [Content Brief]
- [5]. Wu AL, et al. FGF19 regulates cell proliferation, glucose and bile acid metabolism via FGFR4-dependent and independent pathways. PLoS One. 2011 Mar 18;6(3):e17868. [Content Brief]
- [6]. Xie MH, et al. FGF-19, a novel fibroblast growth factor with unique specificity for FGFR4. Cytokine. 1999 Oct;11(10):729-35. [Content Brief]
- [7]. Kim RD, et al. First-in-Human Phase I Study of Fisogatinib (BLU-554) Validates Aberrant FGF19 Signaling as a Driver Event in Hepatocellular Carcinoma. Cancer Discov. 2019 Dec;9(12):1696-1707. [Content Brief]
- [8]. Hagel M, et al. First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway. Cancer Discov. 2015 Apr;5(4):424-37. [Content Brief]
All Product Categories
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FGFR4 Related Products (7)
Related Products (7)
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Dabogratinib (GMP)
0 ImagesCat. No.: HY-159642GCAS No.: 2800223-30-5Synonyms: TYRA-300 (GMP)Dabogratinib (GMP) is the GMP-grade version of Dabogratinib (HY-159642). Dabogratinib (TYRA-300) is an orally active, selective FGFR3 inhibitor with an IC50 of 11 nM. Dabogratinib exhibits antitumor activity against urothelial carcinoma and solid tumors. Dabogratinib downregulates the FGFR3 and ERK1/2 signaling pathways, and induces tumor growth inhibition and regression in FGFR3-altered xenograft models. Dabogratinib promotes chondrocyte proliferation and differentiation, drives endochondral bone formation and overall body growth, partially restores long bone proportions, and improves craniofacial and spinal morphology. Dabogratinib can be used for the research of metastatic urothelial carcinoma, achondroplasia and hypochondroplasia.
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FGFR-IN-27
0 ImagesCat. No.: HY-183780FGFR-IN-27 is an orally active, broad-spectrum FGFR inhibitor, with an IC50 of 0.24 nM against human FGFR1, 0.71 nM against FGFR2, 0.87 nM against FGFR3, and 6.50 nM against FGFR4. FGFR-IN-27 inhibits cancer cell proliferation and blocks tumor growth. FGFR-IN-27 reduces the phosphorylation levels of AKT and ERK, induces apoptosis and ferroptosis, increases ROS levels, and decreases GSH levels. FGFR-IN-27 can be used in the research of hepatocellular carcinoma.
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FGFR-IN-28
0 ImagesCat. No.: HY-184250CAS No.: 2634677-16-8FGFR-IN-28 is a FGFR inhibitor with inhibitory activity against multiple subtypes of the FGFR family, with an IC50 of 4.4 nM against FGFR4. FGFR-IN-28 inhibits kinase activity and phosphorylation processes, and blocks the downstream MAPK and AKT signaling pathways. FGFR-IN-28 induces cellular DNA damage, cell cycle arrest, apoptosis and ferroptosis, and reduces the adhesion, invasion and metastasis abilities of cancer cells. FGFR-IN-28 exhibits anti-tumor activity in in vitro experiments on colon cancer cells, and inhibits tumor growth in colon cancer xenograft models. FGFR-IN-28 can be used in colon cancer-related research.
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FGFR-IN-29
0 ImagesCat. No.: HY-189241FGFR-IN-29 is an orally active pan-FGFR inhibitor that suppresses the kinase activities of FGFR1, FGFR2, FGFR3, and FGFR4. FGFR-IN-29 blocks the intracellular phosphorylation process of FGFR and arrests downstream tumor cell proliferation signaling. FGFR-IN-29 inhibits tumor growth in solid tumor xenograft mouse models. FGFR-IN-29 is applicable for cancer-related research.
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FGFR3-IN-12
0 ImagesCat. No.: HY-181752CAS No.: 3127143-52-3FGFR3-IN-12 is a selective fibroblast growth factor receptor 3 (FGFR3) inhibitor with an IC50 of 6.8 nM. FGFR3-IN-12 shows an IC50 of 19.2 nM against FGFR3V555M and an IC50 of 16.9 nM against TNK1 (Thirty-eight Negative Kinase 1). FGFR3-IN-12 inhibits cancer cells proliferation and induces caspase-mediated apoptosis. FGFR3-IN-12 exhibits antitumor activity in bladder cancer xenografts mice models. FGFR3-IN-12 can be used for the research of cancer, such as bladder cancer.
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CYB-5067
0 ImagesCat. No.: HY-184598CYB-5067 is a FGFR molecular glue degrader with a DC50 of 27 nM against FGFR2. CYB-5067 inhibits FGFR1, FGFR3, FGFR4 and downstream FGFR signaling pathways, induces antiproliferative activity in vitro, and exhibits sustained target protein inhibition in vivo without obvious hook effect. CYB-5067 shows significant tumor growth inhibitory activity in the ETV6-FGFR2 fusion Ba/F3 xenograft model. CYB-5067 can be used for the research of FGFR-driven cancers.
