ArticleVirulence2016
FR-900098, an antimalarial development candidate that inhibits the non-mevalonate isoprenoid biosynthesis pathway, shows no evidence of acute toxicity and genotoxicity.
Article in Virulence, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 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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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Article
- Discovery of Antimicrobial Phosphonopeptide Natural Products from Bacillus velezensis by Genome Mining.Applied and environmental microbiology · 2023Article
- Over 40 Years of Fosmidomycin Drug Research: A Comprehensive Review and Future Opportunities.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Selection of an Aptamer against the Enzyme 1-deoxy-D-xylulose-5-phosphate Reductoisomerase fromPharmaceutics · 2022Article
- Deciphering structure, function and mechanism of Plasmodium IspD homologs from their evolutionary imprints.Journal of computer-aided molecular design · 2019Article
- Remarkable similarity in Plasmodium falciparum and Plasmodium vivax geranylgeranyl diphosphate synthase dynamics and its implication for antimalarial drug design.Chemical biology & drug design · 2018Article
- The High Cost of Stroke and Stroke Cytoprotection Research.Translational stroke research · 2017Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
FR-900098 is an inhibitor of 1-deoxy-d-xylulose-5-phosphate (DXP) reductoisomerase, the second enzyme in the non-mevalonate isoprenoid biosynthesis pathway. In previous studies, FR-900098 was shown to possess potent antimalarial activity in vitro and in a murine malaria model. In order to provide a basis for further preclinical and clinical development, we studied the acute toxicity and genotoxicity of FR-900098. We observed no acute toxicity in rats, i.e. there were no clinical signs of toxicity and no substance-related deaths after the administration of a single dose of 3000 mg/kg body weight orally or 400 mg/kg body weight intravenously. No mutagenic potential was detected in the Salmonella typhimurium reverse mutation assay (Ames test) or an in vitro mammalian cell gene mutation test using mouse lymphoma L5178Y/TK(+/-) cells (clone 3.7.2C), both with and without metabolic activation. In addition, FR-900098 demonstrated no clastogenic or aneugenic capability or significant adverse effects on blood formation in an in vivo micronucleus test with bone marrow erythrocytes from NMRI mice. We conclude that FR-900098 lacks acute toxicity and genotoxicity, supporting its further development as an antimalarial drug.
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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.