{"doi":"10.17615/30dm-mz27","title":"N -Phenylbenzamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore","abstract":"Persistent opening of the mitochondrial permeability transition pore (PTP), an inner membrane channel, leads to mitochondrial dysfunction and renders the PTP a therapeutic target for a host of life-threatening diseases. Herein, we report our effort toward identifying small-molecule inhibitors of this target through structure-activity relationship optimization studies, which led to the identification of several potent analogues around the N-phenylbenzamide compound series identified by high-throughput screening. In particular, compound 4 (3-(benzyloxy)-5-chloro-N-(4-(piperidin-1-ylmethyl)phenyl)benzamide) displayed noteworthy inhibitory activity in the mitochondrial swelling assay (EC50 =280 nm), poor-to-very-good physicochemical as well as in vitro pharmacokinetic properties, and conferred very high calcium retention capacity to mitochondria. From the data, we believe compound 4 in this series represents a promising lead for the development of PTP inhibitors of pharmacological relevance.","journal":"UNC Libraries","year":2020,"id":116054,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"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":542902,"name":"Thomas D.Y. Chung","orcid":"0000-0003-4856-6233","position":1,"is_corresponding":false},{"id":261064,"name":"Michael P. Hedrick","orcid":null,"position":2,"is_corresponding":false},{"id":542903,"name":"Justina Šileikytė","orcid":"0000-0002-6795-6344","position":3,"is_corresponding":false},{"id":274876,"name":"Jeffrey Aubé","orcid":"0000-0003-1049-5767","position":4,"is_corresponding":false},{"id":274870,"name":"Sudeshna Roy","orcid":"0000-0003-0237-4156","position":5,"is_corresponding":false},{"id":542904,"name":"Michael Forte","orcid":"0000-0003-3972-7154","position":6,"is_corresponding":false},{"id":341778,"name":"Frank J. Schoenen","orcid":"0000-0003-2711-1117","position":7,"is_corresponding":false},{"id":543697,"name":"Benjamin Neuenswander","orcid":null,"position":8,"is_corresponding":false},{"id":542901,"name":"Paolo Bernardi","orcid":"0000-0001-9187-3736","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:40.596604Z","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":[]}