ArticleACS chemical biology2015
Experimental and Theoretical Evaluation of the Ethynyl Moiety as a Halogen Bioisostere.
Article in ACS chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed.
- Expanding and Enhancing Neural Network-Based QM-AI Models for the Accurate Prediction of Halogen-π Interaction Energies in Protein Contexts.Journal of chemical information and modeling · 2026Article
- Characterization of the Second-Generation Covalent Fragment Library (CovLib Gen2): Thiol Reactivity Profiling and p53-Y220C Rescue.Drug design, development and therapy · 2026Article
- Design, synthesis and SAR studies of N'-(Ethynylsalicylidene)arenecarbohydrazides as next-generation broad-spectrum antifungal agents.Bioorganic & medicinal chemistry · 2025Article
- Nanomolar inhibitor of the galectin-8 N-terminal domain binds via a non-canonical cation-π interaction.Communications chemistry · 2025Article
- Unconventional C-Hlg···H-C (Hlg = Cl, Br, and I) Interactions Involving Organic Halides: A Theoretical Study.Molecules (Basel, Switzerland) · 2024Article
- Computational Design, Synthesis, and Biological Evaluation of Diimidazole Analogues Endowed with Dual PCSK9/HMG-CoAR-Inhibiting Activity.Journal of medicinal chemistry · 2023Article
- Predicting Blood-Brain Barrier Permeation of Erlotinib and JCN037 by Molecular Simulation.The Journal of membrane biology · 2023Article
- Exploring the Antitubercular Activity of Anthranilic Acid Derivatives: From MabA (FabG1) Inhibition to Intrabacterial Acidification.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Synthesis of Amino Acids Bearing Halodifluoromethyl Moieties and Their Application to p53-Derived Peptides Binding to Mdm2/Mdm4.Drug design, development and therapy · 2023Article
- Revisiting a challenging p53 binding site: a diversity-optimized HEFLib reveals diverse binding modes in T-p53C-Y220C.RSC medicinal chemistry · 2022Article
- Development of a Potent Brain-Penetrant EGFR Tyrosine Kinase Inhibitor against Malignant Brain Tumors.ACS medicinal chemistry letters · 2020Article
- Recent Synthetic Approaches towards Small Molecule Reactivators of p53.Biomolecules · 2020Review
- A structure-guided molecular chaperone approach for restoring the transcriptional activity of the p53 cancer mutant Y220C.Future medicinal chemistry · 2019Article
- Roles of computational modelling in understanding p53 structure, biology, and its therapeutic targeting.Journal of molecular cell biology · 2019Review
- Synthesis and pre-clinical evaluation of a new class of high-affinityEuropean journal of nuclear medicine and molecular imaging · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors.
Funding
Abstract
Bioisosteric replacements are widely used in medicinal chemistry to improve physicochemical and ADME properties of molecules while retaining or improving affinity. Here, using the p53 cancer mutant Y220C as a test case, we investigate both computationally and experimentally whether an ethynyl moiety is a suitable bioisostere to replace iodine in ligands that form halogen bonds with the protein backbone. This bioisosteric transformation is synthetically feasible via Sonogashira cross-coupling. In our test case of a particularly strong halogen bond, replacement of the iodine with an ethynyl group resulted in a 13-fold affinity loss. High-resolution crystal structures of the two analogues in complex with the p53-Y220C mutant enabled us to correlate the different affinities with particular features of the binding site and subtle changes in ligand binding mode. In addition, using QM calculations and analyzing the PDB, we provide general guidelines for identifying cases where such a transformation is likely to improve ligand recognition.
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.