{"doi":"10.3389/fonc.2023.1144153","title":"Virtual screening of ultra-large chemical libraries identifies cell-permeable small-molecule inhibitors of a “non-druggable” target, STAT3 N-terminal domain","abstract":"STAT3 N-terminal domain is a promising molecular target for cancer treatment and modulation of immune responses. However, STAT3 is localized in the cytoplasm, mitochondria, and nuclei, and thus, is inaccessible to therapeutic antibodies. Its N-terminal domain lacks deep pockets on the surface and represents a typical \"non-druggable\" protein. In order to successfully identify potent and selective inhibitors of the domain, we have used virtual screening of billion structure-sized virtual libraries of make-on-demand screening samples. The results suggest that the expansion of accessible chemical space by cutting-edge ultra-large virtual compound databases can lead to successful development of small molecule drugs for hard-to-target intracellular proteins.","journal":"Frontiers in Oncology","year":2023,"id":339635,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":579587,"name":"Cody L. Hoop","orcid":"0000-0003-4441-8321","position":1,"is_corresponding":false},{"id":1074123,"name":"Karen Stefanisko","orcid":null,"position":2,"is_corresponding":false},{"id":325214,"name":"Sergey G. Tarasov","orcid":"0000-0002-7134-0374","position":3,"is_corresponding":false},{"id":1073604,"name":"Sourav Sinha","orcid":"0000-0002-9631-0569","position":4,"is_corresponding":false},{"id":360813,"name":"Marc C. Nicklaus","orcid":"0000-0002-4775-7030","position":5,"is_corresponding":false},{"id":325215,"name":"Nadya I. Tarasova","orcid":"0000-0002-4949-0069","position":6,"is_corresponding":false},{"id":1073603,"name":"Pedro Andrade Bonilla","orcid":"0000-0002-3710-0342","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T01:10:49.535464Z","pmid":"37182134","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":[]}