ReviewNature reviews. Drug discovery2012
The determination and interpretation of the therapeutic index in drug development.
Review in Nature reviews. Drug discovery, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 225 papers, 3 of them syntheses that pooled it.
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
225 citing papers in PubMed, 3 syntheses or guidelines pooled it, 543 citations in OpenAlex.
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- Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization.Expert opinion on drug metabolism & toxicology · 2021Pooled it
- Cytotoxicity of Plant-Mediated Synthesis of Metallic Nanoparticles: A Systematic Review.International journal of molecular sciences · 2018Pooled it
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- Ultra-slow release of hydrophilic drugs via multilamellar-multivesicular liposomes formed by unsaturated phospholipids.Nature biomedical engineering · 2026Article
- Macrolide antibiotic action, resistance, and tolerance, and approaches to improve their activity against Gram-negative bacteria.The Journal of antibiotics · 2026Review
- Quantifying the therapeutic index of acupoints using measurements of effective and hazardous depths.Integrative medicine research · 2026Article
- Acute and sub-acute toxicity assessment of tetrodotoxin in Sprague-Dawley rats following intramuscular injection.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A Comprehensive Review on Engineering Release at the Molecular Level: Role of Functional Groups in Polysaccharide-Based Drug Delivery.Materials (Basel, Switzerland) · 2026Review
- Discovery of potent low-toxicity antimicrobial peptides through diffusion modeling.Nature communications · 2026Article
- Lessons From Drug Discovery for Cryoprotective Agent Design: An AI-Oriented Perspective.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
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- A reversible broad-spectrum antiviral targets the human V-ATPase VResearch square · 2026Article
- Clinical Development of Novel-Novel Multi-Company Combination Therapies in Oncology.Current oncology reports · 2026Review
- Engineering Compact Base Editors by AlphaFold-Guided Mutation Scan and Escherichia coli-Based Tri-Selection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The fluoroquinoline compound exerts anti-erythroleukemic effects by dual-targeting GLUT1 and the PI3K/AKT signaling pathway.Scientific reports · 2026Article
- New Chemical Scaffold with Antimicrobial Activity Identified in a Screening of Industrial Photoactive Compounds.Antibiotics (Basel, Switzerland) · 2026Article
- A simple compound prioritization method for drug discovery considering multi-target binding.Digital discovery · 2026Article
- Enhanced muscle uptake of chemically optimized miR-23b antisense oligonucleotides as lead compounds for myotonic dystrophy type 1.American journal of human genetics · 2026Article
- Discovery of a Novel DNMT1 Inhibitor with Improved Efficacy in Treating β-Thalassemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
165 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A key part of drug discovery and development is the characterization and optimization of the safety and efficacy of drug candidates to identify those that have an appropriately balanced safety-efficacy profile for a given indication. The therapeutic index (TI)--which is typically considered as the ratio of the highest exposure to the drug that results in no toxicity to the exposure that produces the desired efficacy--is an important parameter in efforts to achieve this balance. Various types of safety and efficacy data are generated in vitro and in vivo (in animals and in humans), and these data can be used to predict the clinical TI of a drug candidate at an early stage. However, approaches to systematically and quantitatively compare these types of data and to apply this knowledge more effectively are needed. This article critically discusses the various aspects of TI determination and interpretation in drug development for both small molecule drugs and biotherapeutics.
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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.