{"doi":"10.1371/journal.pone.0230670","title":"Efficacy of a small molecule inhibitor of the transcriptional cofactor PC4 in prevention and treatment of non-small cell lung cancer","abstract":"The human positive coactivator 4 (PC4) was originally identified as a multi-functional cofactor capable of mediating transcription activation by diverse gene- and tissue-specific activators. Recent studies suggest that PC4 might also function as a novel cancer biomarker and therapeutic target for different types of cancers. siRNA knockdown studies indicated that down-regulation of PC4 expression could inhibit tumorigeneicity of A549 non-small cell lung cancer tumor model in nude mice. Here we show that AG-1031, a small molecule identified by high throughput screening, can inhibit the double-stranded DNA binding activity of PC4, more effectively than its single-stranded DNA binding activity. AG-1031 also specifically inhibited PC4-dependent transcriptional activation in vitro using purified transcription factors. AG-1031 inhibited proliferation of several cultured cell lines derived from non-small cell lung cancers (NSCLC) and growth of tumors that formed from A549 cell xenografts in immuno-compromised mice. Moreover, pre-injection of AG-1031 in these mice not only reduced tumor size, but also prevented tumor formation in 20% of the animals. AG-1031 treated A549 cells and tumors from AG-1031 treated animals showed a significant decrease in the levels of both PC4 and VEGFC, a key mediator of angiogenesis in cancer. On the other hand, all tested mice remained constant weight during animal trials. These results demonstrated that AG-1031 could be a potential therapy for PC4-positive NSCLC.","journal":"PLoS ONE","year":2020,"id":110974,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"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":528110,"name":"Andrei Pavlov","orcid":null,"position":1,"is_corresponding":false},{"id":301201,"name":"Sohail Malik","orcid":"0000-0001-8907-1750","position":2,"is_corresponding":false},{"id":45742,"name":"Hong Chen","orcid":"0000-0003-3478-6139","position":3,"is_corresponding":false},{"id":392651,"name":"Nancy Kim","orcid":"0000-0001-9470-636X","position":4,"is_corresponding":false},{"id":245398,"name":"Ziqing Li","orcid":"0000-0003-3596-3520","position":5,"is_corresponding":false},{"id":527194,"name":"Xiaohong Zhang","orcid":"0000-0002-6732-2499","position":6,"is_corresponding":false},{"id":494043,"name":"Melvin Depamphilis","orcid":"0000-0002-9898-5260","position":7,"is_corresponding":false},{"id":246358,"name":"Robert G. Roeder","orcid":"0000-0003-3865-8572","position":8,"is_corresponding":false},{"id":527195,"name":"Hui Ge","orcid":"0000-0002-4950-5021","position":9,"is_corresponding":false},{"id":527193,"name":"Yan Zhang","orcid":"0009-0006-0145-302X","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T23:13:01.914939Z","pmid":"32231397","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":[]}