{"doi":"10.1101/2020.05.24.098665","title":"A screen of FDA-approved drugs identifies inhibitors of Protein Tyrosine Phosphatase 4A3 (PTP4A3 or PRL-3)","abstract":"ABSTRACT Protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) is highly expressed in a variety of cancers, where it promotes tumor cell migration and metastasis leading to poor prognosis. Despite its clinical significance, there are currently no viable options to target PRL-3 in vivo . Here, we screened 1,443 FDA-approved drugs for their ability to inhibit the activity of the PRL phosphatase family. We identified five specific inhibitors for PRL-3 as well as one selective inhibitor of PRL-2. Additionally, we found nine drugs that broadly and significantly suppressed PRL activity. Two of these broad PRL inhibitors, Salirasib and Candesartan blocked PRL-3-induced migration in human embryonic kidney (HEK) cells with no negative impact on cell viability. Both drugs prevented migration of PRL-3 expressing human colorectal cancer cells to a similar degree as the research-grade PRL inhibitor, Thienopyridone, and are selective towards PRLs over other phosphatases. In silico modeling revealed that Salirasib binds a putative allosteric site near the WPD loop of PRL-3, while Candesartan binds a potentially novel targetable site adjacent to the CX 5 R motif. Inhibitor binding at either of these sites is predicted to trap PRL-3 in a closed conformation, preventing substrate binding and inhibiting function.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":123736,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"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":567161,"name":"Mark Vincent C. dela Cerna","orcid":"0000-0001-5995-4667","position":1,"is_corresponding":false},{"id":567162,"name":"Caroline N. Smith","orcid":"0000-0002-1876-7790","position":2,"is_corresponding":false},{"id":567975,"name":"Blaine G. Patty","orcid":null,"position":3,"is_corresponding":false},{"id":567976,"name":"Donghan Lee","orcid":null,"position":4,"is_corresponding":false},{"id":451605,"name":"Jessica S. Blackburn","orcid":"0000-0001-9464-3784","position":5,"is_corresponding":false},{"id":505680,"name":"Dylan R. Rivas","orcid":null,"position":0,"is_corresponding":true}],"reference_count":52,"raw_metadata":null,"created_at":"2026-07-18T23:15:03.403566Z","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":[]}