{"doi":"10.1038/nchembio.137","title":"Small molecule–mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer","abstract":"The pervasive influence of secreted Wnt signaling proteins in tissue homeostasis and tumorigenesis has galvanized efforts to identify small molecules that target Wnt-mediated cellular responses. By screening a diverse synthetic chemical library, we have discovered two new classes of small molecules that disrupt Wnt pathway responses; whereas one class inhibits the activity of Porcupine, a membrane-bound acyltransferase that is essential to the production of Wnt proteins, the other abrogates destruction of Axin proteins, which are suppressors of Wnt/beta-catenin pathway activity. With these small molecules, we establish a chemical genetic approach for studying Wnt pathway responses and stem cell function in adult tissue. We achieve transient, reversible suppression of Wnt/beta-catenin pathway response in vivo, and we establish a mechanism-based approach to target cancerous cell growth. The signal transduction mechanisms shown here to be chemically tractable additionally contribute to Wnt-independent signal transduction pathways and thus could be broadly exploited for chemical genetics and therapeutic goals.","journal":"Nature Chemical Biology","year":2009,"id":802,"datarank":1.0860974541383202,"base_score":7.240649694255466,"endowment":7.240649694255466,"self_citation_contribution":1.0860974541383202,"citation_network_contribution":0.0,"self_endowment_contribution":1.0860974541383202,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1394,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0478,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2009-01-04","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":7755,"name":"Michael E Dodge","orcid":null,"position":1,"is_corresponding":false},{"id":7756,"name":"Wei Tang","orcid":"0000-0002-2662-217X","position":2,"is_corresponding":false},{"id":7757,"name":"Jianming Lu","orcid":null,"position":3,"is_corresponding":false},{"id":7758,"name":"Zhiqiang Ma","orcid":"0000-0002-3983-6636","position":4,"is_corresponding":false},{"id":7759,"name":"Chih-Wei Fan","orcid":null,"position":5,"is_corresponding":false},{"id":7760,"name":"Shuguang Wei","orcid":"0000-0001-5737-2647","position":6,"is_corresponding":false},{"id":7761,"name":"Wayne Hao","orcid":null,"position":7,"is_corresponding":false},{"id":7762,"name":"Jessica Kilgore","orcid":null,"position":8,"is_corresponding":false},{"id":7763,"name":"Noelle S. Williams","orcid":"0000-0003-1894-5742","position":9,"is_corresponding":false},{"id":7764,"name":"Michael G. Roth","orcid":"0000-0002-9056-332X","position":10,"is_corresponding":false},{"id":7765,"name":"James F. Amatruda","orcid":"0000-0002-9901-2137","position":11,"is_corresponding":false},{"id":7766,"name":"Chuo Chen","orcid":"0000-0002-3118-4901","position":12,"is_corresponding":false},{"id":7767,"name":"Lawrence Lum","orcid":"0000-0002-6119-0253","position":13,"is_corresponding":false},{"id":7768,"name":"Michael Dodge","orcid":null,"position":14,"is_corresponding":false},{"id":7769,"name":"Wei‐Jen Tang","orcid":"0000-0002-8267-8995","position":15,"is_corresponding":false},{"id":7770,"name":"Jianming Lü","orcid":"0000-0002-3794-641X","position":16,"is_corresponding":false},{"id":7771,"name":"Jessica A. Kilgore","orcid":"0000-0001-9138-2099","position":17,"is_corresponding":false},{"id":7754,"name":"Baozhi Chen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","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":[]}