FGFRs are hot targets due to their function on cell survival, proliferation, migration, and angiogenesis, while most of these studies focus on FGFR1, FGFR2 and FGFR3. There is growing evidence suggested that FGFR4 plays an important and unique role in oncogenesis, tumor progression and anti-tumor therapy in many types of cancer. Abnormal expression of FGFR4, including, FGFR4 overexpression, FGF ligand overexpression, FGFR4 somatic hotspot mutations, and the FGFR4 G388R single nucleotide polymorphism, play different roles in development of cancer.
Fibroblast growth factor receptor 4 (FGFR4), also known as cluster of differentiation 334 (CD334), is one of a family of highly conserved tyrosine kinase receptors, which consists of a cellular ligand domain, a single transmembrane helixdomain, and a cytoplasmic domain with tyrosine kinase activity. FGFR4 is a protein encoded by the FGFR4 gene, which contains a unique amino acid in the kinase domain, the C552 residue.
FGFR4 is widely expressed in the embryonic stage, participating in tissue differentiation and organogenesis. After birth,the function of FGFR4 is restrained to actively growing tissue, including liver, lung and bone, to regulate bile acid production, metabolism, muscle differentiation, and tissue repair.
FGFR4 participates in the regulation of many signaling pathways. Canonical FGFR4 signaling pathways is dependent on FGF ligand binding, which causes tyrosine phosphorylation in the intracellular domain of FGFRs. A pro-growth and anti-apoptotic state are achieved through canonical FGFR4 activation. Besides, there are several non-canonical ways to activate FGFR4, thereby regulate cell proliferation, migration, morphological changes and even the invasion and metastasis of tumor cells.
FGFR4 is reportedly overexpressed in various cancers, such as breast, prostate, hepatocellular, ovarian, gastric, colorectal, and pancreatic cancer, where it may contribute to tumor progression. Inhibition of FGFR4 suppresses the aggressiveness of gastric, colorectal, and serous ovarian cancers that are high grade.
Approved Drugs
Ponatinib, lenvatinib, heparin, erdafitinib, pemigatinib, etc.
Drugs in Development
FGF401, BLU-554, H3B-6527, NCT02325739, etc.
Protein Tyrosine Kinase Activity
Ponatinib, lenvatinib, heparin, etc.
Compound Binding to The C552 Residue
FGF401, BLU-554, H3B-6527, NCT02325739, etc.
Anti-FGFR4 Monoclonal Antibody
U3–1784, LD1, etc.
Hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia, nausea, pyrexia, thrombocytopenia, anemia, neutropenia, lymphopenia, leukopenia, stomatitis, palmar-plantar erythrodysethesia syndrome and proteinuria.
Lenvatinib plus everolimus treats advanced renal cell carcinoma.
CD BioSciences provides FGFR4 testing services by Elisa, WB, IP, or IF assay. The results of FGFR4 testing are used to evaluate the activities of candidates against FGFR4 or targeted diseases. You can choose one or more testing ways to detect the level of FGFR4 according to your experiment.
The goal of early drug discovery is to find novel lead compounds that have the desired potency, selectivity, and ADMET properties for pre-clinical evaluation.
CD BioSciences offers hit identification services to make your find targeted compounds more successful and faster.
Antibody drugs exhibit many incomparable advantages, such as the high specificity, affinity, and efficiency, which is an emerging direction on targeted drug development.
CD BioSciences provides comprehensive services on FGFR4-targeted antibody drugs development with professional technology, extensive experience, and advanced equipment.
We will make a specific experimental plan according to your requirements, including but not limited to
We will make specific disease models to accelerate your targeted drug discovery project, including but not limited to
CD BioSciences will establish the specific disease model according to your requirements to evaluate the inhibitory activity of your candidates targeted FGFR4. We have various cell lines and the species of our animal models cover rats, mice, rabbits, dogs, and non-human primates.