ArticleChemMedChem2015
Discovery, Synthesis, and Optimization of Diarylisoxazole-3-carboxamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore.
Article in ChemMedChem, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 42 citations in OpenAlex.
- Spiropiperidine-Based Oligomycin-Analog Ligands To Counteract the Ischemia-Reperfusion Injury in a Renal Cell Model.Journal of medicinal chemistry · 2024Article
- Modeling Human Muscular Dystrophies in Zebrafish: Mutant Lines, Transgenic Fluorescent Biosensors, and Phenotyping Assays.International journal of molecular sciences · 2023Review
- Modulation and Pharmacology of the Mitochondrial Permeability Transition: A Journey from F-ATP Synthase to ANT.Molecules (Basel, Switzerland) · 2021Review
- Skeletal Muscle Mitochondria Dysfunction in Genetic Neuromuscular Disorders with Cardiac Phenotype.International journal of molecular sciences · 2021Review
- Targeting the Mitochondrial Permeability Transition Pore to Prevent Age-Associated Cell Damage and Neurodegeneration.Oxidative medicine and cellular longevity · 2021Review
- Physiopathology of the Permeability Transition Pore: Molecular Mechanisms in Human Pathology.Biomolecules · 2020Review
- A novel class of cardioprotective small-molecule PTP inhibitors.Pharmacological research · 2020Article
- Mitochondrial function in the heart: the insight into mechanisms and therapeutic potentials.British journal of pharmacology · 2019Review
- Pharmacological modulation of mitochondrial ion channels.British journal of pharmacology · 2019Review
- Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies.International journal of molecular sciences · 2019Review
- The Mitochondrial Permeability Transition in Mitochondrial Disorders.Oxidative medicine and cellular longevity · 2019Review
- Targeting Mitochondrial Ion Channels to Fight Cancer.International journal of molecular sciences · 2018Review
- The unique histidine in OSCP subunit of F-ATP synthase mediates inhibition of the permeability transition pore by acidic pH.EMBO reports · 2018Article
- Mitochondrial permeability transition in cardiac ischemia-reperfusion: whether cyclophilin D is a viable target for cardioprotection?Cellular and molecular life sciences : CMLS · 2017Review
- CaEMBO reports · 2017Article
- A small-molecule DS44170716 inhibits CaScientific reports · 2017Article
- Identification of ER-000444793, a Cyclophilin D-independent inhibitor of mitochondrial permeability transition, using a high-throughput screen in cryopreserved mitochondria.Scientific reports · 2016Article
- Calcium and reactive oxygen species in regulation of the mitochondrial permeability transition and of programmed cell death in yeast.Cell calcium · 2016Review
- Shutting down the pore: The search for small molecule inhibitors of the mitochondrial permeability transition.Biochimica et biophysica acta · 2016Review
- N-Phenylbenzamides as Potent Inhibitors of the Mitochondrial Permeability Transition Pore.ChemMedChem · 2016Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
The mitochondrial permeability transition pore (mtPTP) is a Ca(2+) -requiring mega-channel which, under pathological conditions, leads to the deregulated release of Ca(2+) and mitochondrial dysfunction, ultimately resulting in cell death. Although the mtPTP is a potential therapeutic target for many human pathologies, its potential as a drug target is currently unrealized. Herein we describe an optimization effort initiated around hit 1, 5-(3-hydroxyphenyl)-N-(3,4,5-trimethoxyphenyl)isoxazole-3-carboxamide, which was found to possess promising inhibitory activity against mitochondrial swelling (EC50 <0.39 μM) and showed no interference on the inner mitochondrial membrane potential (rhodamine 123 uptake EC50 >100 μM). This enabled the construction of a series of picomolar mtPTP inhibitors that also potently increase the calcium retention capacity of the mitochondria. Finally, the therapeutic potential and in vivo efficacy of one of the most potent analogues, N-(3-chloro-2-methylphenyl)-5-(4-fluoro-3-hydroxyphenyl)isoxazole-3-carboxamide (60), was validated in a biologically relevant zebrafish model of collagen VI congenital muscular dystrophies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.