ArticleNature chemical biology2011
A yeast-based screen reveals that sulfasalazine inhibits tetrahydrobiopterin biosynthesis.
Article in Nature chemical biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 122 citations in OpenAlex.
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- Saccharomyces cerevisiae as a model for mammalian diseases.FEMS yeast research · 2026Review
- Pain Hypersensitivity and Increased Urinary Tetrahydrobiopterin Levels in Mice Submitted to High-Fat Diet.Brain sciences · 2025Article
- A Simplified Guide RNA Synthesis Protocol for SNAP- and Halo-Tag-Based RNA Editing Tools.Molecules (Basel, Switzerland) · 2025Article
- Target immobilization on glass microfiber membranes as a label-free strategy for hit identification.Analytical and bioanalytical chemistry · 2023Article
- Chemical tags and beyond: Live-cell protein labeling technologies for modern optical imaging.Smart molecules : open access · 2023Review
- Peripheralized sepiapterin reductase inhibition as a safe analgesic therapy.Frontiers in pharmacology · 2023Review
- Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Kinetic and Structural Characterization of the Self-Labeling Protein Tags HaloTag7, SNAP-tag, and CLIP-tag.Biochemistry · 2021Article
- Turning liabilities into opportunities: Off-target based drug repurposing in cancer.Seminars in cancer biology · 2021Review
- Sepiapterin reductase: Characteristics and role in diseases.Journal of cellular and molecular medicine · 2020Review
- Review
- Quantitative analysis of amino acid metabolism in liver cancer links glutamate excretion to nucleotide synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Sepiapterin Reductase Inhibition Leading to Selective Reduction of Inflammatory Joint Pain in Mice and Increased Urinary Sepiapterin Levels in Humans and Mice.Arthritis & rheumatology (Hoboken, N.J.) · 2020Article
- Repurposing of Tranilast for Potential Neuropathic Pain Treatment by Inhibition of Sepiapterin Reductase in the BHACS omega · 2019Article
- Monitoring structural modulation of redox-sensitive proteins in cells with MS-CETSA.Redox biology · 2019Article
- Cystine-glutamate antiporter xCT deficiency suppresses tumor growth while preserving antitumor immunity.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Polyamine synthesis as a target ofThe Journal of biological chemistry · 2018Review
- Methods to validate Hsp90 inhibitor specificity, to identify off-target effects, and to rethink approaches for further clinical development.Cell stress & chaperones · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We introduce an approach for detection of drug-protein interactions that combines a new yeast three-hybrid screening for identification of interactions with affinity chromatography for their unambiguous validation. We applied the methodology to the profiling of clinically approved drugs, resulting in the identification of previously known and unknown drug-protein interactions. In particular, we were able to identify off-targets for erlotinib and atorvastatin, as well as an enzyme target for the anti-inflammatory drug sulfasalazine. We demonstrate that sulfasalazine and its metabolites, sulfapyridine and mesalamine, are inhibitors of the enzyme catalyzing the final step in the biosynthesis of the cofactor tetrahydrobiopterin. The interference with tetrahydrobiopterin metabolism provides an explanation for some of the beneficial and deleterious properties of sulfasalazine and furthermore suggests new and improved therapies for the drug. This work thus establishes a powerful approach for drug profiling and provides new insights in the mechanism of action of clinically approved drugs.
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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.