{"doi":"10.1002/ange.202101328","title":"Discovery of a Potent Degrader for Fibroblast Growth Factor Receptor 1/2","abstract":"Abstract Aberrant activation of FGFR signaling occurs in many cancers, and ATP‐competitive FGFR inhibitors have received regulatory approval. Despite demonstrating clinical efficacy, these inhibitors exhibit dose‐limiting toxicity, potentially due to a lack of selectivity amongst the FGFR family and are poorly tolerated. Here, we report the discovery and characterization of DGY‐09‐192, a bivalent degrader that couples the pan‐FGFR inhibitor BGJ398 to a CRL2 VHL E3 ligase recruiting ligand, which preferentially induces FGFR1&2 degradation while largely sparing FGFR3&4. DGY‐09‐192 exhibited two‐digit nanomolar DC 50 s for both wildtype FGFR2 and several FGFR2‐fusions, resulting in degradation‐dependent antiproliferative activity in representative gastric cancer and cholangiocarcinoma cells. Importantly, DGY‐09‐192 induced degradation of a clinically relevant FGFR2 fusion protein in a xenograft model. Taken together, we demonstrate that DGY‐09‐192 has potential as a prototype FGFR degrader.","journal":"Angewandte Chemie","year":2021,"id":206397,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9477,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":299770,"name":"Jie Jiang","orcid":"0000-0003-3795-672X","position":1,"is_corresponding":false},{"id":634872,"name":"Qibiao Wu","orcid":"0000-0002-1670-1050","position":2,"is_corresponding":false},{"id":255570,"name":"Nathaniel J. Henning","orcid":"0000-0003-0504-6481","position":3,"is_corresponding":false},{"id":299772,"name":"Katherine A. Donovan","orcid":"0000-0002-8539-5106","position":4,"is_corresponding":false},{"id":560556,"name":"Hong Yue","orcid":"0000-0003-4347-3193","position":5,"is_corresponding":false},{"id":243062,"name":"Jianwei Che","orcid":"0000-0003-4956-4811","position":6,"is_corresponding":false},{"id":33142,"name":"Wenchao Lu","orcid":"0000-0003-1175-365X","position":7,"is_corresponding":false},{"id":262829,"name":"Eric S. Fischer","orcid":"0000-0001-7337-6306","position":8,"is_corresponding":false},{"id":50927,"name":"Nabeel Bardeesy","orcid":"0000-0003-3867-0416","position":9,"is_corresponding":false},{"id":226576,"name":"Tinghu Zhang","orcid":"0000-0003-1028-8020","position":10,"is_corresponding":false},{"id":226581,"name":"Nathanael S. Gray","orcid":"0000-0001-5354-7403","position":11,"is_corresponding":false},{"id":228754,"name":"Guangyan Du","orcid":"0000-0002-6413-8741","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-18T23:51:41.571653Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}