ArticleJournal of the American Chemical Society2019
The Alkyne Moiety as a Latent Electrophile in Irreversible Covalent Small Molecule Inhibitors of Cathepsin K.
Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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
48 citing papers in PubMed, 112 citations in OpenAlex.
- Increased Bone Resorption during Lactation in Pycnodysostosis.International journal of molecular sciences · 2021Trial
- Lidocaine inhibits osteoclast activity in vitro.Bone reports · 2026Article
- Article
- Antiviral drug discovery and development: challenges and future directions.Signal transduction and targeted therapy · 2026Review
- Mechanism-based inactivation of human aldehyde oxidase by erlotinib: Mechanistic insights from structural analogs and molecular docking.Molecular pharmacology · 2026Article
- Advancing Covalent Ligand and Drug Discovery beyond Cysteine.Chemical reviews · 2025Review
- Macromolecular crystallography at Elettra: current and future perspectives.Journal of synchrotron radiation · 2025Article
- Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus MScience advances · 2025Article
- Design, Construction, and Validation of a Yeast-Displayed Chemically Expanded Antibody Library.ACS synthetic biology · 2025Article
- Development of potential immunomodulatory ligands targeting natural killer T cells inspired by gut symbiont-derived glycolipids.Communications chemistry · 2025Article
- Article
- Cathepsin K Inhibitors as Potential Drugs for the Treatment of Osteoarthritis.International journal of molecular sciences · 2025Review
- Emerging opportunities for intact and native protein analysis using chemical proteomics.Analytica chimica acta · 2025Review
- Mechanistic Insights into Nitrile and Alkyne Covalent Inhibitors of the SARS-CoV-2 Main Protease.ACS catalysis · 2025Article
- Development and Application of Reversible and Irreversible Covalent Probes for Human and Mouse Cathepsin-K Activity Detection, Revealing Nuclear Activity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Design, Construction, and Validation of a Yeast-Displayed Chemically Expanded Antibody Library.bioRxiv : the preprint server for biology · 2024Article
- Functionalizing tandem mass tags for streamlining click-based quantitative chemoproteomics.Communications chemistry · 2024Article
- Electrophilic Compounds in the Human Diet and Their Role in the Induction of the Transcription Factor NRF2.International journal of molecular sciences · 2024Review
- Calpeptin is a potent cathepsin inhibitor and drug candidate for SARS-CoV-2 infections.Communications biology · 2023Article
- Solid-Phase Compatible Silane-Based Cleavable Linker Enables Custom Isobaric Quantitative Chemoproteomics.Journal of the American Chemical Society · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Irreversible covalent inhibitors can have a beneficial pharmacokinetic/pharmacodynamics profile but are still often avoided due to the risk of indiscriminate covalent reactivity and the resulting adverse effects. To overcome this potential liability, we introduced an alkyne moiety as a latent electrophile into small molecule inhibitors of cathepsin K (CatK). Alkyne-based inhibitors do not show indiscriminate thiol reactivity but potently inhibit CatK protease activity by formation of an irreversible covalent bond with the catalytic cysteine residue, confirmed by crystal structure analysis. The rate of covalent bond formation ( k
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.