FGFR3
FGFR3 encodes a receptor tyrosine kinase that acts as a negative regulator of endochondral bone growth by limiting chondrocyte proliferation, hypertrophic differentiation, and osteogenesis in growth plate cartilage[1][2]. Mechanistically, activated FGFR3 signaling inhibits bone growth through MAPK-dependent suppression of chondrocyte differentiation and STAT1-associated suppression of chondrocyte proliferation[3]. In skeletal disease models, activating FGFR3 mutations explain achondroplasia as gain-of-function lesions that intensify this inhibitory growth-control program[1]. In cancer, activating FGFR3 mutations occur in bladder and cervix carcinomas, and FGFR3-TACC3 fusions show oncogenic activity in glioblastoma models[4][5]. Compared with related isoforms, alternative splicing of the FGFR3 IgIII domain generates IIIb/IIIc variants with distinct ligand-binding properties, and FGFR3 IIIb binds only acidic FGF in the reported binding assays[6]. For experimental and translational applications, erdafitinib, an FGFR1-4 tyrosine kinase inhibitor, produced clinical activity in advanced urothelial carcinoma with susceptible FGFR2/3 alterations and later improved overall survival versus chemotherapy after anti-PD-1/PD-L1 treatment[7][8].
References:
- [1]. Deng C, et al. Fibroblast growth factor receptor 3 is a negative regulator of bone growth. Cell. 1996;84(6):911-921.
- [2]. Wang Q, Green RP, Zhao G, Ornitz DM. Differential regulation of endochondral bone growth and joint development by FGFR1 and FGFR3 tyrosine kinase domains. Development. 2001 Oct;128(19):3867-76. [Content Brief]
- [3]. Murakami S, et al. Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype. Genes Dev. 2004 Feb 1;18(3):290-305. [Content Brief]
- [4]. Cappellen D, et al. Frequent activating mutations of FGFR3 in human bladder and cervix carcinomas. Nat Genet. 1999 Sep;23(1):18-20. [Content Brief]
- [5]. Singh D, et al. Transforming fusions of FGFR and TACC genes in human glioblastoma. Science. 2012 Sep 7;337(6099):1231-5. [Content Brief]
- [6]. Chellaiah AT, et al. Fibroblast growth factor receptor (FGFR) 3. Alternative splicing in immunoglobulin-like domain III creates a receptor highly specific for acidic FGF/FGF-1. J Biol Chem. 1994 Apr 15;269(15):11620-7. [Content Brief]
- [7]. Loriot Y, et al. Erdafitinib in Locally Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2019 Jul 25;381(4):338-348. [Content Brief]
- [8]. Loriot Y, et al. Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2023 Nov 23;389(21):1961-1971. [Content Brief]
All Product Categories
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FGFR3 Related Products (7)
Related Products (7)
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IMC-D11
0 ImagesCat. No.: HY-P991106Purity: 98.51%Synonyms: LY-3076226 antibodyIMC-D11 (LY-3076226 antibody) is an anti-FGFR3 IgG1 monoclonal antibody with an EC50 of approximately 0.1 nM against hFGFR3b and hFGFR3c. IMC-D11 inhibits the growth of FGFR3-dependent lung adenocarcinoma in mouse models and shows no effect on tumors that do not express FGFR3. IMC-D11 can serve as an ADC Antibody for ADC synthesis, such as LY3076226. IMC-D11 is applicable to research related to urothelial carcinoma, multiple myeloma, lung adenocarcinoma, as well as advanced or metastatic cancers.
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LC-MF-4
0 ImagesCat. No.: HY-174981Purity: 98.05%LC-MF-4 is a selective FGFR3 PROTAC degrader with a DC50 of 30.89 nM in KMS-11 cells. LC-MF-4 inhibits the metabolic function of FGFR3-TACC3 fusion positive cancers with reduction of ATP synthesis and inhibition of mitochondrial biogenesis genes. LC-MF-4 has potent antitumor activity in the Ba/F3-FGFR3-TACC3 xenograft mice model. LC-MF-4 can be used for FGFR3-altered cancers like bladder cancer and urothelial carcinoma (UC) research. Pink: FGFR3 ligand (HY-175414); Blue: VHL ligase ligand (HY-125905); Black: linker (HY-Y1224)
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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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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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FGFR-IN-12
0 ImagesCat. No.: HY-160013CAS No.: 943189-02-4FGFR-IN-12 (example 14), a pyrimidinyl aryl urea derivative, is a potent FGFR inhibitor.
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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.
