ArticleJournal of medicinal chemistry2014
Discovery of potent and specific dihydroisoxazole inhibitors of human transglutaminase 2.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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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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
18 citing papers in PubMed, 52 citations in OpenAlex.
- Targeted Lysosomal Degradation of Secreted and Cell Surface Proteins through the LRP-1 Pathway.Journal of the American Chemical Society · 2023Article
- Discovery and Characterization of PROTACs Targeting Tissue Transglutaminase (TG2).Journal of medicinal chemistry · 2023Article
- Covalent Inhibition by a Natural Product-Inspired Latent Electrophile.Journal of the American Chemical Society · 2023Article
- The war on hTG2: warhead optimization in small molecule human tissue transglutaminase inhibitors.RSC medicinal chemistry · 2023Article
- LRP-1 links post-translational modifications to efficient presentation of celiac disease-specific T cell antigens.Cell chemical biology · 2023Article
- Fragment-Based Discovery of a Novel, Brain Penetrant, Orally Active HDAC2 Inhibitor.ACS medicinal chemistry letters · 2022Article
- Type 2 Transglutaminase in Coeliac Disease: A Key Player in Pathogenesis, Diagnosis and Therapy.International journal of molecular sciences · 2022Review
- Probing tissue transglutaminase mediated vascular smooth muscle cell aging using a novel transamidation-deficient Tgm2-C277S mouse model.Cell death discovery · 2021Article
- Interplay between Type 2 Transglutaminase (TG2), Gliadin Peptide 31-43 and Anti-TG2 Antibodies in Celiac Disease.International journal of molecular sciences · 2020Review
- An efficient 3-acylquinoline synthesis from acetophenones and anthranilRSC advances · 2019Article
- Cystamine and cysteamine as inhibitors of transglutaminase activityBioscience reports · 2018Review
- Cystamine and Disulfiram Inhibit Human Transglutaminase 2 via an Oxidative Mechanism.Biochemistry · 2018Article
- Cardiac fibrosis can be attenuated by blocking the activity of transglutaminase 2 using a selective small-molecule inhibitor.Cell death & disease · 2018Article
- Transglutaminase 2 in human diseases.BioMedicine · 2017Article
- Thioredoxin-1 Selectively Activates Transglutaminase 2 in the Extracellular Matrix of the Small Intestine: IMPLICATIONS FOR CELIAC DISEASE.The Journal of biological chemistry · 2017Article
- Intracellular TG2 Activity Increases Microtubule Stability but is not Sufficient to Prompt Neurite Growth.Neuroscience bulletin · 2017Article
- Coeliac disease and gluten-related disorders in childhood.Nature reviews. Gastroenterology & hepatology · 2015Review
- Therapeutic approaches for celiac disease.Best practice & research. Clinical gastroenterology · 2015Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Transglutaminase 2 (TG2) is a ubiquitously expressed enzyme that catalyzes the posttranslational modification of glutamine residues on protein or peptide substrates. A growing body of literature has implicated aberrantly regulated activity of TG2 in the pathogenesis of various human inflammatory, fibrotic, and other diseases. Taken together with the fact that TG2 knockout mice are developmentally and reproductively normal, there is growing interest in the potential use of TG2 inhibitors in the treatment of these conditions. Targeted-covalent inhibitors based on the weakly electrophilic 3-bromo-4,5-dihydroisoxazole (DHI) scaffold have been widely used to study TG2 biology and are well tolerated in vivo, but these compounds have only modest potency, and their selectivity toward other transglutaminase homologues is largely unknown. In the present work, we first profiled the selectivity of existing inhibitors against the most pertinent TG isoforms (TG1, TG3, and FXIIIa). Significant cross-reactivity of these small molecules with TG1 was observed. Structure-activity and -selectivity analyses led to the identification of modifications that improved potency and isoform selectivity. Preliminary pharmacokinetic analysis of the most promising analogues was also undertaken. Our new data provides a clear basis for the rational selection of dihydroisoxazole inhibitors as tools for in vivo biological investigation.
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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.