ArticleJournal of medicinal chemistry2012
Selective and potent urea inhibitors of cryptosporidium parvum inosine 5'-monophosphate dehydrogenase.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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.
The trial behind it
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
24 citing papers in PubMed, 49 citations in OpenAlex.
- 30th Annual GPPharmaceuticals (Basel, Switzerland) · 2023Article
- The Enzymatic Activity of Inosine 5'-Monophosphate Dehydrogenase May Not Be a Vulnerable Target forACS infectious diseases · 2021Article
- Eco-friendly methoximation of aromatic aldehydes and ketones using MnClRoyal Society open science · 2021Article
- Molecular Basis of P131 Cryptosporidial-IMPDH Selectivity-A Structural, Dynamical and Mechanistic Stance.Cell biochemistry and biophysics · 2021Article
- A probable means to an end: exploring P131 pharmacophoric scaffold to identify potential inhibitors of Cryptosporidium parvum inosine monophosphate dehydrogenase.Journal of molecular modeling · 2021Article
- Mycophenolic anilides as broad specificity inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors.Bioorganic & medicinal chemistry letters · 2020Article
- Evaluation of Bronopol and Disulfiram as PotentialMolecules (Basel, Switzerland) · 2020Article
- Genetic ablation of purine salvage inProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Inhibitors of inosine 5'-monophosphate dehydrogenase as emerging new generation antimicrobial agents.MedChemComm · 2019Review
- A suite of phenotypic assays to ensure pipeline diversity when prioritizing drug-like Cryptosporidium growth inhibitors.Nature communications · 2019Article
- Expanding Benzoxazole-Based Inosine 5'-Monophosphate Dehydrogenase (IMPDH) Inhibitor Structure-Activity As Potential Antituberculosis Agents.Journal of medicinal chemistry · 2018Article
- Benzoxazoles, Phthalazinones, and Arylurea-Based Compounds with IMP Dehydrogenase-Independent Antibacterial Activity against Francisella tularensis.Antimicrobial agents and chemotherapy · 2017Article
- Review of Experimental Compounds Demonstrating Anti-Toxoplasma Activity.Antimicrobial agents and chemotherapy · 2016Review
- Inhibition of Inosine-5'-monophosphate Dehydrogenase from Bacillus anthracis: Mechanism Revealed by Pre-Steady-State Kinetics.Biochemistry · 2016Article
- Structure of Cryptosporidium IMP dehydrogenase bound to an inhibitor with in vivo antiparasitic activity.Acta crystallographica. Section F, Structural biology communications · 2015Article
- A novel cofactor-binding mode in bacterial IMP dehydrogenases explains inhibitor selectivity.The Journal of biological chemistry · 2015Article
- Drug Development Against the Major Diarrhea-Causing Parasites of the Small Intestine, Cryptosporidium and Giardia.Frontiers in microbiology · 2015Review
- Mycobacterium tuberculosis IMPDH in Complexes with Substrates, Products and Antitubercular Compounds.PloS one · 2015Article
- Synthesis, in vitro evaluation and cocrystal structure of 4-oxo-[1]benzopyrano[4,3-c]pyrazole Cryptosporidium parvum inosine 5'-monophosphate dehydrogenase (CpIMPDH) inhibitors.Journal of medicinal chemistry · 2014Article
- Repurposing cryptosporidium inosine 5'-monophosphate dehydrogenase inhibitors as potential antibacterial agents.ACS medicinal chemistry letters · 2014Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Cryptosporidium parvum and related species are zoonotic intracellular parasites of the intestine. Cryptosporidium is a leading cause of diarrhea in small children around the world. Infection can cause severe pathology in children and immunocompromised patients. This waterborne parasite is resistant to common methods of water treatment and therefore a prominent threat to drinking and recreation water even in countries with strong water safety systems. The drugs currently used to combat these organisms are ineffective. Genomic analysis revealed that the parasite relies solely on inosine-5'-monophosphate dehydrogenase (IMPDH) for the biosynthesis of guanine nucleotides. Herein, we report a selective urea-based inhibitor of C. parvum IMPDH (CpIMPDH) identified by high-throughput screening. We performed a SAR study of these inhibitors with some analogues exhibiting high potency (IC(50) < 2 nM) against CpIMPDH, excellent selectivity >1000-fold versus human IMPDH type 2 and good stability in mouse liver microsomes. A subset of inhibitors also displayed potent antiparasitic activity in a Toxoplasma gondii model.
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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.