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]

FGFR4 Inhibitors (3)

FGFR4 Related Products (3):

By Type:	Pan (1) Selective (2)

Cat. No.	Product Name	Effect	Purity

HY-183780

FGFR-IN-27	Inhibitor
FGFR-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.

HY-184250

FGFR-IN-28	Inhibitor
FGFR-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.

HY-183909

EphB1-IN-2	Inhibitor
EphB1-IN-2 is a mutant-selective kinase inhibitor of ABL and FGFR4, with an IC₅₀ of 14 nM against ABL^G321C mutant and 163 nM against FGFR4^G556C mutant. EphB1-IN-2 shows selectively over wild-type ABL and FGFR4.

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