Ask about this productRelated genes to: FGFR2 antibody
- Gene:
- FGFR2 NIH gene
- Name:
- fibroblast growth factor receptor 2
- Previous symbol:
- KGFR, BEK, CFD1, JWS
- Synonyms:
- CEK3, TK14, TK25, ECT1, K-SAM, CD332
- Chromosome:
- 10q26.13
- Locus Type:
- gene with protein product
- Date approved:
- 1991-05-09
- Date modifiied:
- 2019-04-23
Related products to: FGFR2 antibody
Related articles to: FGFR2 antibody
- Molecular glue degraders (MGDs) have emerged as a transformative therapeutic modality, offering the potential to deplete undruggable or pathogenic proteins. However, the rational design of MGDs remains inherently challenging compared to traditional heterobifunctional degraders. Recently, the implementation of transposable chemical gluing handles has provided an efficient approach to convert established protein-targeting ligands into target-specific MGDs. In this study, by incorporating diverse molecular glue handles and amino acid-based degrons into the solvent-exposed exit vectors of infigratinib, we synthesized a library of 30 candidate MGDs. Preliminary screening and subsequent lead optimization identified LC-MG-5 and LC-MG-10 as highly efficient degraders of FGFR2. In cellular models, both compounds demonstrated potent suppression of FGFR2-mediated signaling pathways. Mechanistic investigations revealed that the covalent engagement of the gluing handle is a critical determinant for successful proteasomal degradation of FGFR2. This work provides a framework for the rational transformation of kinase inhibitors into covalent molecular glue degraders, underscoring the potential of FGFR degradation as a next-generation precision medicine strategy for FGFR2-driven malignancies. - Source: PubMed
Publication date: 2026/06/02
Cao XianshengHuang XiaohaoSong ChongranShi ShuZhu YongjuanZheng LuluLiang GuangChen Lingfeng - Fibroblast growth factor receptors 2 and 3 (FGFR2/3) are attractive therapeutic targets in multiple human cancers. Here, we report the discovery of a series of tricyclic 1-(4-amino-5-ethynyl-8,9-dihydropyrazino[1',2':1,5]pyrrolo[2,3-]pyrimidin-7(6)-yl)prop-2-en-1-one derivatives as novel covalent FGFR2/3 inhibitors through structure-based design and optimization. The lead compound, , potently suppressed FGFR2- or FGFR3-driven Ba/F3 cells (IC = 1.1 nM and 0.20 nM), with reduced activity against Ba/F3-FGFR1 cells (IC = 17.1 nM) and parental Ba/F3 cells (IC > 1000 nM). In a panel of 416 kinases, selectively inhibited FGFR2/3 kinases, including clinically relevant mutants. Covalent modification of FGFR2/3 was confirmed by mass spectrometry and X-ray crystallography. Functionally, selectively suppressed the proliferation of FGFR2-dependent cancer cell lines, dose-dependently inhibited FGFR2 downstream signaling, and induced apoptosis in an FGFR2-dependent manner. Moreover, demonstrated favorable oral bioavailability (56%) in rats and achieved significant tumor growth inhibition in an SNU-16 gastric cancer xenograft model. - Source: PubMed
Publication date: 2026/06/08
Lu XuzhiTian ZhaodiLi XueqiangChen XiaojuanTien Jean Ching-YiYang YayuanYin YueLi QingrunHuang WeixueZhou FengtaoZhang JinweiRen XiaomeiLiu DanTodd Abigail JLi ShuqinChen YonghengChinnaiyan Arul MChang ShaohuaDing KeWang Zhen - Craniosynostosis is defined by premature cranial suture fusion and is biologically heterogeneous. To map mitochondrial-associated signals in craniosynostosis and rank follow-up candidates, we integrated two public microarray datasets (GSE27976, GSE50796), corrected batch effects, and analyzed 14,186 shared genes using limma. This identified 798 nominal DEGs (388 upregulated and 410 downregulated), of which 19 remained significant after Benjamini-Hochberg correction. Intersecting the nominal DEG list with the MitoCarta 3.0 inventory yielded 24 mitochondrial DEGs (MitoDEGs). Complementary feature selection reduced these 24 MitoDEGs to an eight-gene panel (TMEM11, SLC25A21, GPT2, CYP27A1, MRPS30, ACAA2, GSR, and LIG3); a multigene score reached an apparent AUC of 0.806 in the integrated dataset. Correlation-based co-expression analyses linked the panel to mitochondrial translation, electron transport, amino-acid metabolism, redox control, and cell-matrix signaling. Among craniosynostosis cases, consensus clustering on the eight genes separated two molecular subtypes with distinct GSVA pathway profiles. For experimental support in a genetically defined mouse model, we profiled bilateral coronal suture complexes from Fgfr2C361Y/+ knock-in (KI) pups and WT littermates. Jess capillary immunoassay showed higher CYP27A1 abundance in KI sutures (P = 0.0276), whereas ACAA2, LIG3, MRPS30, and TMEM11 were not significant. Data-independent acquisition (DIA) proteomics identified 523 differentially abundant proteins (516 increased, 7 decreased in KI), followed by stricter-threshold reporting, sensitivity analysis, and threshold-free rank-based enrichment. MitoCarta proteins and mitochondrial pathways remained supported under these more conservative analyses. These results support mitochondria-associated transcriptomic and proteomic changes in craniosynostosis and prioritize a limited set of mitochondrial candidates for future mechanistic work. - Source: PubMed
Publication date: 2026/06/08
Zeng HanWang YuDong MiaoYue YingyingJin Xiaolei - Hyperphosphatemia is a recognized on-target adverse event of erdafitinib, a pan-fibroblast growth factor receptor (pan-FGFR) tyrosine kinase inhibitor with Food and Drug Administration approval to treat advanced urothelial cell carcinoma with FGFR2/3 mutations. This study hypothesized that hyperphosphatemia is a biomarker for drug activity and is associated with improved overall survival (OS) and other oncologic end points in phase 2/3 clinical trials. - Source: PubMed
Zhu DenzelSteidle MatthewJia YufeiCheng ZijingGuercio Brendan JBandari JathinMalshy Kamil - Fibroblast growth factor receptors (FGFR) are tyrosine kinases that regulate cellular responses including proliferation, survival, and migration. FGFR fusion genes arose from chromosomal translocations or deletions, lead to ligand-independent constitutive signal activation and contribute to carcinogenesis and cancer progression. FGFR2 fusion genes are identified in 7.4-13.6% of intrahepatic cholangiocarcinoma and 3.6% of perihilar cholangiocarcinoma. They are also reported in colorectal, prostate, and breast cancers, though at lower frequencies. Diagnosis methods are RT-PCR, RNA sequencing, FISH, and NGS. Comprehensive genomic profiling (CGP) tests are available clinically. Three FGFR inhibitors are currently approved. Pemigatinib (approved in 2021) demonstrated a response rate of 35.5%, futibatinib (approved in 2023) showed a response rate of 42%, and tasurgratinib (approved in 2024) achieved a response rate of 30.2%. The most common adverse event is hyperphosphatemia. Alopecia, diarrhea, nail disorders, and retinal detachment are also required attention. Polyclonal on-target resistance to pan-FGFR inhibitors and increasing of FGFR2 kinase domain resistance mutations based on treatment history has been reported. Novel therapeutics, such as highly selective FGFR2 inhibitors and next-generation inhibitors, are developed and are expected to improve prognosis for patients with FGFR2 fusion-positive solid tumors. - Source: PubMed
Kokuryo ToshioMizuno TakashiOnoe ShunsukeSunagawa MasakiWatanabe NobuyukiBaba TaisukeYamada MihokoKurimoto KeisukeKawakatsu ShojiEbata Tomoki