ArticleJournal of medicinal chemistry2011
Potent, selective, and orally available benzoisothiazolone phosphomannose isomerase inhibitors as probes for congenital disorder of glycosylation Ia.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 47 citations in OpenAlex.
- Iso- and Benzisothiazolinone Inhibitors of Monoacylglycerol Lipase: Exploring On-Target Activity Through Scaffold Decoration and In Situ Warhead Generation.ChemMedChem · 2026Article
- Recent Advances in the Synthesis of Benzo[Molecules (Basel, Switzerland) · 2025Review
- Article
- Mannose controls mesoderm specification and symmetry breaking in mouse gastruloids.Developmental cell · 2024Article
- Congenital disorders of glycosylation: narration of a story through its patents.Orphanet journal of rare diseases · 2023Review
- Genetic validation of Aspergillus fumigatus phosphoglucomutase as a viable therapeutic target in invasive aspergillosis.The Journal of biological chemistry · 2022Article
- Recent advances in sulfur-nitrogen bond formationRSC advances · 2018Review
- CDG Therapies: From Bench to Bedside.International journal of molecular sciences · 2018Review
- Inhibition ofChemical science · 2016Article
- Avoiding Fluorescence Assay Interference-The Case for Diaphorase.Assay and drug development technologies · 2016Review
- Design, synthesis and evaluation of benzoisothiazolones as selective inhibitors of PHOSPHO1.Bioorganic & medicinal chemistry letters · 2014Article
- Mannose phosphate isomerase regulates fibroblast growth factor receptor family signaling and glioma radiosensitivity.PloS one · 2014Article
- Ebsulfur is a benzisothiazolone cytocidal inhibitor targeting the trypanothione reductase of Trypanosoma brucei.The Journal of biological chemistry · 2013Article
- Therapies and therapeutic approaches in Congenital Disorders of Glycosylation.Glycoconjugate journal · 2013Review
- Neurology of inherited glycosylation disorders.The Lancet. Neurology · 2012Article
- Endocrine manifestations related to inherited metabolic diseases in adults.Orphanet journal of rare diseases · 2012Review
- Phosphomannose isomerase inhibitors improve N-glycosylation in selected phosphomannomutase-deficient fibroblasts.The Journal of biological chemistry · 2011Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
We report the discovery and validation of a series of benzoisothiazolones as potent inhibitors of phosphomannose isomerase (PMI), an enzyme that converts mannose-6-phosphate (Man-6-P) into fructose-6-phosphate (Fru-6-P) and, more importantly, competes with phosphomannomutase 2 (PMM2) for Man-6-P, diverting this substrate from critical protein glycosylation events. In congenital disorder of glycosylation type Ia, PMM2 activity is compromised; thus, PMI inhibition is a potential strategy for the development of therapeutics. High-throughput screening (HTS) and subsequent chemical optimization led to the identification of a novel class of benzoisothiazolones as potent PMI inhibitors having little or no PMM2 inhibition. Two complementary synthetic routes were developed, enabling the critical structural requirements for activity to be determined, and the compounds were subsequently profiled in biochemical and cellular assays to assess efficacy. The most promising compounds were also profiled for bioavailability parameters, including metabolic stability, plasma stability, and permeability. The pharmacokinetic profile of a representative of this series (compound 19; ML089) was also assessed, demonstrating the potential of this series for in vivo efficacy when dosed orally in disease models.
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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.