ArticleACS chemical biology2017
Rapid Chagas Disease Drug Target Discovery Using Directed Evolution in Drug-Sensitive Yeast.
Article in ACS chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- The heme A synthase Cox15, as a target of redox-active 3-benzylmenadiones with antiparasitic activity.Antimicrobial agents and chemotherapy · 2026Article
- Development of a high throughput cytochrome P450 ligand-binding assay.The Journal of biological chemistry · 2024Article
- Candida albicans' inorganic phosphate transport and evolutionary adaptation to phosphate scarcity.PLoS genetics · 2024Article
- In vitro evolution and whole genome analysis to study chemotherapy drug resistance in haploid human cells.Scientific reports · 2024Article
- Article
- State-of-the-Art in the Drug Discovery Pathway for Chagas Disease: A Framework for Drug Development and Target Validation.Research and reports in tropical medicine · 2023Review
- Identification of Leucinostatins fromACS omega · 2022Article
- Novel mutation in hexokinase 2 confers resistance to 2-deoxyglucose by altering protein dynamics.PLoS computational biology · 2022Article
- Adaptive laboratory evolution in S. cerevisiae highlights role of transcription factors in fungal xenobiotic resistance.Communications biology · 2022Article
- Chemical Cartography Approaches to Study Trypanosomatid Infection.Journal of visualized experiments : JoVE · 2022Article
- Endogenous Sterol Synthesis Is Dispensable forFrontiers in microbiology · 2022Article
- Citronellal Exerts Its Antifungal Activity by Targeting Ergosterol Biosynthesis inJournal of fungi (Basel, Switzerland) · 2021Article
- Article
- MutantHuntWGS: A Pipeline for IdentifyingG3 (Bethesda, Md.) · 2020Article
- Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway.Nature communications · 2020Article
- 3-pyridyl inhibitors with novel activity against Trypanosoma cruzi reveal in vitro profiles can aid prediction of putative cytochrome P450 inhibition.Scientific reports · 2018Article
- Development of a Potent Inhibitor of the Plasmodium Proteasome with Reduced Mammalian Toxicity.Journal of medicinal chemistry · 2017Article
- Evolve and survive.Nature reviews. Microbiology · 2017Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
Recent advances in cell-based, high-throughput phenotypic screening have identified new chemical compounds that are active against eukaryotic pathogens. A challenge to their future development lies in identifying these compounds' molecular targets and binding modes. In particular, subsequent structure-based chemical optimization and target-based screening require a detailed understanding of the binding event. Here, we use directed evolution and whole-genome sequencing of a drug-sensitive S. cerevisiae strain to identify the yeast ortholog of TcCyp51, lanosterol-14-alpha-demethylase (TcCyp51), as the target of MMV001239, a benzamide compound with activity against Trypanosoma cruzi, the etiological agent of Chagas disease. We show that parasites treated with MMV0001239 phenocopy parasites treated with another TcCyp51 inhibitor, posaconazole, accumulating both lanosterol and eburicol. Direct drug-protein binding of MMV0001239 was confirmed through spectrophotometric binding assays and X-ray crystallography, revealing a binding site shared with other antitrypanosomal compounds that target Cyp51. These studies provide a new probe chemotype for TcCyp51 inhibition.
Indexed as
Identifiers
What OpenQuestion holds
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.