ArticleBioorganic & medicinal chemistry letters2009
Novel non-active site inhibitor of Cryptosporidium hominis TS-DHFR identified by a virtual screen.
Article in Bioorganic & medicinal chemistry letters, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Molecular pathogenesis of Cryptosporidium and advancements in therapeutic interventions.Parasite (Paris, France) · 2025Review
- Targeting the TS dimer interface in bifunctional Cryptosporidium hominis TS-DHFR from parasitic protozoa: Virtual screening identifies novel TS allosteric inhibitors.Bioorganic & medicinal chemistry letters · 2020Article
- Structure activity relationship towards design of cryptosporidium specific thymidylate synthase inhibitors.European journal of medicinal chemistry · 2019Article
- Novel allosteric covalent inhibitors of bifunctional Cryptosporidium hominis TS-DHFR from parasitic protozoa identified by virtual screening.Bioorganic & medicinal chemistry letters · 2019Article
- Understanding the molecular mechanism of substrate channeling and domain communication in protozoal bifunctional TS-DHFR.Protein engineering, design & selection : PEDS · 2017Review
- Alanine mutants of the interface residues of human thymidylate synthase decode key features of the binding mode of allosteric anticancer peptides.Journal of medicinal chemistry · 2015Article
- Virtual screening reveals allosteric inhibitors of the Toxoplasma gondii thymidylate synthase-dihydrofolate reductase.Bioorganic & medicinal chemistry letters · 2014Article
- Integrated text mining and chemoinformatics analysis associates diet to health benefit at molecular level.PLoS computational biology · 2014Article
- Article
- Exploring novel strategies for AIDS protozoal pathogens: α-helix mimetics targeting a key allosteric protein-protein interaction inMedChemComm · 2013Article
- Selective peptide inhibitors of bifunctional thymidylate synthase-dihydrofolate reductase from Toxoplasma gondii provide insights into domain-domain communication and allosteric regulation.Protein science : a publication of the Protein Society · 2013Article
- Prodrug activation by Cryptosporidium thymidine kinase.The Journal of biological chemistry · 2010Article
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Authors and funding
7 authors.
Funding
Abstract
The essential enzyme thymidylate synthase-dihydrofolate reductase (TS-DHFR) is a validated drug target for many pathogens, but has been elusive in Cryptosporidium hominis, as active site inhibitors of the enzymes from related parasitic protozoa show decreased potency and lack of species specificity over the human enzymes. As a rational approach to discover novel inhibitors, we conducted a virtual screen of a non-active site pocket in the DHFR linker region. From this screen, we have identified and characterized a noncompetitive inhibitor, flavin mononucleotide (FMN), with micromolar potency that is selective for ChTS-DHFR versus the human enzymes. These results describe a novel allosteric pocket amenable to inhibitor targeting, and a lead compound with which to move towards potent, selective inhibitors of ChTS-DHFR.
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Registered trials
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