2. Signaling Pathways
  3. Protein Tyrosine Kinase/RTK
  4. FGFR
  5. FGFR3 Isoform

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].

FGFR3 Related Products (4):

Cat. No. Product Name Effect Purity
  • HY-174981
    LC-MF-4
    		Degrader
    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)
  • 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-160013
    FGFR-IN-12
    		Inhibitor
    FGFR-IN-12 (example 14), a pyrimidinyl aryl urea derivative, is a potent FGFR inhibitor.