{"doi":"10.1002/anie.202003500","title":"Mutant‐Selective Allosteric EGFR Degraders are Effective Against a Broad Range of Drug‐Resistant Mutations","abstract":"Targeting epidermal growth factor receptor (EGFR) through an allosteric mechanism provides a potential therapeutic strategy to overcome drug-resistant EGFR mutations that emerge within the ATP binding site. Here, we develop an allosteric EGFR degrader, DDC-01-163, which can selectively inhibit the proliferation of L858R/T790M (L/T) mutant Ba/F3 cells while leaving wildtype EGFR Ba/F3 cells unaffected. DDC-01-163 is also effective against osimertinib-resistant cells with L/T/C797S and L/T/L718Q EGFR mutations. When combined with an ATP-site EGFR inhibitor, osimertinib, the anti-proliferative activity of DDC-01-163 against L858R/T790M EGFR-Ba/F3 cells is enhanced. Collectively, DDC-01-163 is a promising allosteric EGFR degrader with selective activity against various clinically relevant EGFR mutants as a single agent and when combined with an ATP-site inhibitor. Our data suggests that targeted protein degradation is a promising drug development approach for mutant EGFR.","journal":"Angewandte Chemie International Edition","year":2020,"id":52138,"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":140,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":227591,"name":"Ciric To","orcid":"0000-0002-6333-3174","position":1,"is_corresponding":false},{"id":265183,"name":"Dries J.H. De Clercq","orcid":null,"position":2,"is_corresponding":false},{"id":262827,"name":"Eunyoung Park","orcid":"0000-0001-5618-1267","position":3,"is_corresponding":false},{"id":265184,"name":"Charles M. Ponthier","orcid":null,"position":4,"is_corresponding":false},{"id":227608,"name":"Bo Hee Shin","orcid":"0000-0001-8790-7382","position":5,"is_corresponding":false},{"id":229703,"name":"Mierzhati Mushajiang","orcid":null,"position":6,"is_corresponding":false},{"id":262828,"name":"Radosław P. Nowak","orcid":"0000-0002-0605-0071","position":7,"is_corresponding":false},{"id":262829,"name":"Eric S. Fischer","orcid":"0000-0001-7337-6306","position":8,"is_corresponding":false},{"id":86336,"name":"Michael J. Eck","orcid":"0000-0003-4247-9403","position":9,"is_corresponding":false},{"id":35301,"name":"Pasi A. Jänne","orcid":"0000-0002-7821-4928","position":10,"is_corresponding":false},{"id":226581,"name":"Nathanael S. Gray","orcid":"0000-0001-5354-7403","position":11,"is_corresponding":false},{"id":262826,"name":"Jaebong Jang","orcid":"0000-0002-7962-3395","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":null,"created_at":"2026-07-18T20:42:26.843314Z","pmid":"32510788","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":[]}