ArticleJournal of medicinal chemistry2012
Methyl effects on protein-ligand binding.
Article in Journal of medicinal chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 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.
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
107 citing papers in PubMed.
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- Chemotherapeutic Potential of Fluorouracil-Platinum (IV) Prodrugs Against Cisplatin-Resistant Colorectal Cancer Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Methyl on the Bridge: 2-Methyl Propellane as Precursor for 1,3-Substituted 2-Methylated Bicyclo[1.1.1]Pentanes.Chemistry (Weinheim an der Bergstrasse, Germany) · 2026Article
- Structural basis for the subtype-selective activation of KStructure (London, England : 1993) · 2026Article
- Novel Fluorinated Chlorhexidine Analogues Overcome Resistance in Gram-Negative Bacteria.ACS omega · 2026Article
- Formaldehyde hydrazone as a methyl reagent for nickel-catalyzed cross-coupling methylation of aryl and heteroaryl electrophiles.Nature communications · 2026Article
- Reversible Myeloperoxidase Inhibition by Benzodioxole Carboxamides: Insights from In Silico and InVitro Studies.Cell biochemistry and biophysics · 2026Article
- Thermodynamic Data Remain a Hot Tip for Decoding Binding Affinity and Water Impact on Protein-Ligand Complex Formation to Assist Lead Optimization.Journal of medicinal chemistry · 2026Review
- Discovery of VU6083859, a TAOK1 Selective Inhibitor, and VU6080195, aACS chemical neuroscience · 2026Article
- Parallels between the chloro and methoxy groups for potency optimization.RSC medicinal chemistry · 2026Article
- Multifunctional N-substituted 2-pyridylbenzothiazole derivatives: singlet oxygen generation, protein binding, and photoactivated anticancer and antibacterial activities.RSC advances · 2025Article
- Prediction of enzyme inhibition (ICJournal of molecular modeling · 2025Article
- Late-Stage Heteroarene Alkylation via Minisci Reaction with Gaseous Alkanes Enabled by Hydrogen Atom Transfer in Flow.ACS central science · 2025Article
- Short Scalable Route to Bis-morpholine Spiroacetals and Oxazepane Analogues: Useful 3D-Scaffolds for Compound Library Assembly.The Journal of organic chemistry · 2025Article
- Discovery of CLPP-1071 as an Exceptionally Potent and Orally Efficacious Human ClpP Activator with Strong In Vivo Antitumor Activity.Journal of medicinal chemistry · 2024Article
- Metallaphotocatalytic triple couplings for modular synthesis of elaborate N-trifluoroalkyl anilines.Nature communications · 2024Article
47 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
4 authors.
Funding
Abstract
The effects of addition of a methyl group to a lead compound on biological activity are examined. A literature analysis of >2000 cases reveals that an activity boost of a factor of 10 or more is found with an 8% frequency, and a 100-fold boost is a 1 in 200 event. Four cases in the latter category are analyzed in depth to elucidate any unusual aspects of the protein-ligand binding, distribution of water molecules, and changes in conformational energetics. The analyses include Monte Carlo/free-energy perturbation (MC/FEP) calculations for methyl replacements in inhibitor series for p38α MAP kinase, ACK1, PTP1B, and thrombin. Methyl substitutions ortho to an aryl ring can be particularly effective at improving activity by inducing a propitious conformational change. The greatest improvements in activity arise from coupling the conformational gain with the burial of the methyl group in a hydrophobic region of the protein.
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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.