{"doi":"10.3390/biom12040531","title":"A Novel Allosteric Inhibitor Targets PLK1 in Triple Negative Breast Cancer Cells","abstract":"While Polo-like kinase 1 (PLK1) inhibitors have shown promise in clinical settings for treating triple-negative breast cancer tumors and other solid tumors, they are limited by their ability to bind non-selectively to the ATP kinase domain. Therefore, we sought to develop a PLK1 allosteric inhibitor targeting the PLK1 T-loop (a switch responsible for activation) and evaluate its effects in triple-negative breast cancer cells. A novel compound, RK-10, was developed based on an in silico model, and its effects on specificity, viability, migration, and cell cycle regulation in MCF-10A and MDA-MB 231 cells were evaluated. When MDA-MB 231 cells were treated with 0−50 µg/mL RK-10, phospho-PLK1 (Thr-210) was decreased in cells cultured adherently and cells cultured as mammospheres. RK-10 significantly inhibited viability after 24 h; however, by 48 h, 25−50 µM RK-10 caused >50% reduction. RK-10 attenuated wound healing by up to 99.7% and caused S and G2/M cell cycle arrest, which was associated with increased p21 expression. We developed a novel allosteric inhibitor which mediates anti-proliferative and anti-migratory properties through targeting phospho-PLK1 (Thr-210) in mammospheres and causing S phase and G2/M cell cycle arrest. Further development of PLK1 allosteric inhibitors may be a promising approach for TNBC treatment.","journal":"Biomolecules","year":2022,"id":289208,"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":0.9581,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":970843,"name":"Prasad Thangavelu","orcid":null,"position":1,"is_corresponding":false},{"id":970844,"name":"Renee M. Terrell","orcid":null,"position":2,"is_corresponding":false},{"id":970845,"name":"Bridg’ette Israel","orcid":null,"position":3,"is_corresponding":false},{"id":970403,"name":"A. Sarkar","orcid":"0000-0002-3873-4531","position":4,"is_corresponding":false},{"id":527347,"name":"A. Michael Davidson","orcid":"0000-0002-7831-8532","position":5,"is_corresponding":false},{"id":402649,"name":"Kun Zhang","orcid":"0000-0002-1915-788X","position":6,"is_corresponding":false},{"id":939569,"name":"Rahul Khupse","orcid":null,"position":7,"is_corresponding":false},{"id":527349,"name":"Syreeta L. Tilghman","orcid":"0000-0003-3215-1252","position":8,"is_corresponding":false},{"id":528173,"name":"Jankiben Patel","orcid":null,"position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-19T00:30:18.766838Z","pmid":"35454120","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":[]}