ReviewAccounts of chemical research2009
Efficient drug lead discovery and optimization.
Review in Accounts of chemical research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 261 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
261 citing papers in PubMed, 651 citations in OpenAlex.
- A Dynamics-Informed Machine Learning Framework for Inhibitor Optimization Against Quickly Evolving Targets to Avoid Resistance.bioRxiv : the preprint server for biology · 2026Article
- Article
- Integrating AI in Medicinal Chemistry for Accelerated Drug Discovery: A Comprehensive SAR (CSAR) Optimization Strategy and Discovery of Potent ALDH3A1 Inhibitors.Journal of medicinal chemistry · 2026Article
- Large-Scale Collaborative Assessment of Binding Free Energy Calculations for Drug Discovery Using OpenFE.Journal of chemical information and modeling · 2026Article
- NEMAT: An Automated Nonequilibrium Free-Energy Framework for Predicting Ligand Affinity in Membrane Proteins.Journal of chemical information and modeling · 2026Article
- Dual-LAO for calculating fast and robust relative binding free energies of simple and complex transformations.Communications chemistry · 2026Article
- Natural Products in Epilepsy Treatment: From Traditional Medicine Towards Computational Drug Discovery.Current issues in molecular biology · 2026Review
- Doing More with Less: Accurate and Scalable Ligand Free Energy Calculations by Focusing on the Binding Site.Journal of chemical information and modeling · 2026Article
- Rethinking Nature's Pharmacy: AI Era and Natural Product Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Expanding the Palette of Molecular Fragments for Small Molecule De Novo Design Through Isosteric Swapping.Journal of computational chemistry · 2026Article
- Computational Strategies Reshaping Modern Drug Discovery.Molecules (Basel, Switzerland) · 2026Article
- Advances in 4-Hydroxycoumarin Chemistry: Functionalization, Prominent 4-Hydroxycoumarin-based Therapeutics and their Pharmacological Significance.Mini reviews in medicinal chemistry · 2026Review
- Computational Pipeline for Accelerating the Design of Glycomimetics.Journal of chemical information and modeling · 2025Article
- In Silico Optimization of Inhibitors of the 3-Chymotrypsin-like Protease of SARS-CoV-2.Life (Basel, Switzerland) · 2025Article
- Synthesis, crystal structure, anticancer activity and computational studies of novel Pyrazolo[4',3':5,6]pyrano[2,3-Future medicinal chemistry · 2025Article
- Unlocking the chemistry facilitated by enzymes that process nucleic acids using quantum mechanical and combined quantum mechanics-molecular mechanics techniques.Pure and applied chemistry. Chimie pure et appliquee · 2025Review
- Target-aware 3D molecular generation based on guided equivariant diffusion.Nature communications · 2025Article
- From Molecules to Medicines: The Role of AI-Driven Drug Discovery Against Alzheimer's Disease and Other Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2025Review
- In-silico 3D molecular editing through physics-informed and preference-aligned generative foundation models.Nature communications · 2025Article
- Hybrid Uracil Derivatives with Caffeine and Gramine Obtained via Click Chemistry as Potential Antioxidants and Inhibitors of Plant Pathogens.Molecules (Basel, Switzerland) · 2025Article
201 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
During the 1980s, advances in the abilities to perform computer simulations of chemical and biomolecular systems and to calculate free energy changes led to the expectation that such methodology would soon show great utility for guiding molecular design. Important potential applications included design of selective receptors, catalysts, and regulators of biological function including enzyme inhibitors. This time also saw the rise of high-throughput screening and combinatorial chemistry along with complementary computational methods for de novo design and virtual screening including docking. These technologies appeared poised to deliver diverse lead compounds for any biological target. As with many technological advances, realization of the expectations required significant additional effort and time. However, as summarized here, striking success has now been achieved for computer-aided drug lead generation and optimization. De novo design using both molecular growing and docking are illustrated for lead generation, and lead optimization features free energy perturbation calculations in conjunction with Monte Carlo statistical mechanics simulations for protein-inhibitor complexes in aqueous solution. The specific applications are to the discovery of non-nucleoside inhibitors of HIV reverse transcriptase (HIV-RT) and inhibitors of the binding of the proinflammatory cytokine MIF to its receptor CD74. A standard protocol is presented that includes scans for possible additions of small substituents to a molecular core, interchange of heterocycles, and focused optimization of substituents at one site. Initial leads with activities at low-micromolar concentrations have been advanced rapidly to low-nanomolar inhibitors.
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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.