title: Shutting down the pore: The search for small molecule inhibitors of the mitochondrial permeability transition.
abstract: The mitochondrial permeability transition pore (PTP) is now recognized as playing a key role in a wide variety of human diseases whose common pathology may be based in mitochondrial dysfunction. Recently, PTP assays have been adapted to high-throughput screening approaches to identify small molecules specifically inhibiting the PTP. Following extensive secondary chemistry, the most potent inhibitors of the PTP described to date have been developed. This review will provide an overview of each of these screening efforts, use of resulting compounds in animal models of PTP-based diseases, and problems that will require further study. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padova I-35131, Italy.
authors.forename: Justina
authors.initials: J
authors.lastname: Šileikytė
authors.affiliation: Vollum Institute, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: forte@ohsu.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Forte
mesh_terms: D000813:Anilides / Q000138:chemical synthesis / Q000494:pharmacology; D001550:Benzamidines / Q000138:chemical synthesis / Q000494:pharmacology; D016572:Cyclosporine / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D057166:High-Throughput Screening Assays; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects* / Q000378:metabolism; D000083162:Mitochondrial Permeability Transition Pore; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology; D011806:Quinolinium Compounds / Q000737:chemistry / Q000494:pharmacology; D012632:Secosteroids / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000813:Anilides; D001550:Benzamidines; D007555:Isoxazoles; C000609419:JW47 compound; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D010091:Oximes; D010456:Peptides, Cyclic; D011806:Quinolinium Compounds; D012632:Secosteroids; C549911:3,5-seco-4-norcholestan-5-one oxime-3-ol; D016572:Cyclosporine; C090438:(melle-4)cyclosporin; C499715:alisporivir
keywords: High-throughput; Inhibitors; Mitochondria; Permeability transition; Screening