{"doi":"10.26434/chemrxiv.12091176","title":"Targeted Degradation of Oncogenic KRASG12C by VHL-recruiting PROTACs","abstract":"<p>We report the development of LC-2, the first PROTAC capable of degrading endogenous KRAS<sup>G12C</sup>.<sup> </sup> LC-2 covalently binds KRAS<sup>G12C</sup> with a MRTX849 warhead and recruits the E3 ligase VHL, inducing rapid and sustained KRAS<sup>G12C</sup> degradation leading to suppression of MAPK signaling in both homozygous and heterozygous KRAS<sup>G12C</sup> cell lines. LC-2 demonstrates that PROTAC-mediated degradation is a viable option for attenuating oncogenic KRAS levels and downstream signaling in cancer cells.</p>","journal":"ChemRxiv","year":2020,"id":120413,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"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":472066,"name":"Ling Chu","orcid":"0000-0002-4418-6850","position":1,"is_corresponding":false},{"id":229622,"name":"Dhanusha A. Nalawansha","orcid":null,"position":2,"is_corresponding":false},{"id":555990,"name":"Ke Li","orcid":"0000-0002-5555-3871","position":3,"is_corresponding":false},{"id":107240,"name":"Craig M. Crews","orcid":"0000-0002-8456-2005","position":4,"is_corresponding":false},{"id":555989,"name":"Michael J. Bond","orcid":"0000-0001-9552-4525","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:14:33.640077Z","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":[]}