ReviewCurrent topics in medicinal chemistry2017
Targeting Non-Catalytic Cysteine Residues Through Structure-Guided Drug Discovery.
Review in Current topics in medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed, 73 citations in OpenAlex.
- Advances in the design and discovery of small-molecule tyrosine kinase inhibitors for breast cancer.RSC advances · 2026Review
- Igalan attenuates sepsis-induced inflammation through covalent targeting of the NLRP3 inflammasome pathway.RSC chemical biology · 2026Article
- Application of a MALDI mass spectrometry assay to identify covalent fragments targeting the methyl-lysine reader protein MPP8.SLAS discovery : advancing life sciences R & D · 2026Article
- SCaN: A Screening and Characterization Platform for Nanosuspensions Enables In Vivo Delivery of a Crystalline hRpn13ACS pharmacology & translational science · 2026Article
- Discovery of ATX968: An Orally Available Allosteric Inhibitor of DHX9.Journal of medicinal chemistry · 2025Article
- Robust proteome profiling of cysteine-reactive fragments using label-free chemoproteomics.Nature communications · 2025Article
- A Top-Down Proteomic Assay to Evaluate KRAS4B-Compound Engagement.Analytical chemistry · 2024Article
- Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy.Cancer communications (London, England) · 2024Review
- Covalent targeting of non-cysteine residues in PI4KIIIβ.RSC chemical biology · 2023Article
- Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein-Protein Interaction from Nonselective Fragments.Journal of the American Chemical Society · 2023Article
- Species-specific lipophilicities of fluorinated diketones in complex equilibria systems and their potential as multifaceted reversible covalent warheads.Communications chemistry · 2023Article
- Computer-Aided Drug Design of Novel Derivatives of 2-Amino-7,9-dihydro-8H-purin-8-one as Potent Pan-Janus JAK3 Inhibitors.Molecules (Basel, Switzerland) · 2023Article
- Engaging a Non-catalytic Cysteine Residue Drives Potent and Selective Inhibition of Caspase-6.Journal of the American Chemical Society · 2023Article
- Cysteine Pathogenic Variants of PMM2 Are Sensitive to Environmental Stress with Loss of Structural Stability.Oxidative medicine and cellular longevity · 2023Article
- Enzymatic and Microbial Electrochemistry: Approaches and Methods.ACS measurement science au · 2022Review
- A loss-of-function cysteine mutant in fibulin-3 (EFEMP1) forms aberrant extracellular disulfide-linked homodimers and alters extracellular matrix composition.Human mutation · 2022Article
- Structure-guided design and characterization of a clickable, covalent PARP16 inhibitor.Chemical science · 2022Article
- Cysteine Oxidation in Proteins: Structure, Biophysics, and Simulation.Biochemistry · 2022Review
- Allosteric Hotspots in the Main Protease of SARS-CoV-2.Journal of molecular biology · 2022Article
- Inhibiting a dynamic viral protease by targeting a non-catalytic cysteine.Cell chemical biology · 2022Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The targeting of non-catalytic cysteine residues with small molecules is drawing increased attention from drug discovery scientists and chemical biologists. From a biological perspective, genomic and proteomic studies have revealed the presence of cysteine mutations in several oncogenic proteins, suggesting both a functional role for these residues and also a strategy for targeting them in an 'allele specific' manner. For the medicinal chemist, the structure-guided design of cysteine- reactive molecules is an appealing strategy to realize improved selectivity and pharmacodynamic properties in drug leads. Finally, for chemical biologists, the modification of cysteine residues provides a unique means to probe protein structure and allosteric regulation. Here, we review three applications of cysteinemodifying small molecules: 1) the optimization of existing drug leads, 2) the discovery of new lead compounds, and 3) the use of cysteine-reactive molecules as probes of protein dynamics. In each case, structure-guided design plays a key role in determining which cysteine residue(s) to target and in designing compounds with the proper geometry to enable both covalent interaction with the targeted cysteine and productive non-covalent interactions with nearby protein residues.
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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.