ArticleACS chemical biology2021
Selective Neutral pH Inhibitor of Cathepsin B Designed Based on Cleavage Preferences at Cytosolic and Lysosomal pH Conditions.
Article in ACS chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 55 citations in OpenAlex.
- Lack of cathepsin B increases severity in Niemann-Pick disease, type C1 mice.Neuroscience letters · 2026Article
- Evaluation of Darifenacin for T-Cell Acute Lymphoblastic Leukemia: Selective Targeting of the Non-Neuronal Cholinergic System and Lysosomal Cathepsins.International journal of molecular sciences · 2026Article
- Identification of serum protein biomarkers in individuals with Niemann-Pick disease, type C1.Biomarker research · 2026Article
- Morphable 'Stitched' Sensors for Simultaneous Spatiotemporal Tracking of Correlated Bioanalytes in Living Cells.JACS Au · 2026Article
- mspms: an R package and GUI for multiplex substrate profiling by mass spectrometry.BMC bioinformatics · 2026Article
- Macrophage reprogramming through scavenger receptor-guided and cathepsin B-triggered nanodelivery: from intracellular mechanisms to translational applications.Frontiers in immunology · 2026Review
- Production of human cathepsins using Expi293™ mammalian cell expression system for off-target activity of cysteine protease inhibitor screening.Protein science : a publication of the Protein Society · 2025Article
- The pH-Dependent Specificity of Cathepsin S and Its Implications for Inflammatory Communications and Disease.Biochemistry · 2025Article
- Neutral pH-Selective Inhibition of Cytosolic Cathepsin B: A Novel Drug Targeting Strategy for Traumatic Brain Injury and Alzheimer's Disease.ACS chemical biology · 2025Review
- Lysosomal targeting of liposomes with acidic pH and Cathepsin B induces protein aggregate clearance.Cell communication and signaling : CCS · 2025Article
- Tumor-specific biochemical nanoconversion of self-assembled peptide-conjugated paclitaxel-docetaxel-based nanoparticles.Nano convergence · 2025Article
- Activation of Cytosolic Cathepsin B Activity in the Brain by Traumatic Brain Injury and Inhibition by the Neutral pH Selective Inhibitor Probe Z-Arg-Lys-AOMK.ACS chemical neuroscience · 2025Article
- Mitigating dithiothreitol interference to gold/thiol interface in electrochemical detection of cathepsin B activity toward multiplex protease analysis.Biosensors & bioelectronics · 2025Article
- Cathepsin B prevents cell death by fragmentation and destruction of pathological amyloid fibrils.Cell death discovery · 2025Article
- Production, Purification, and Biochemical Characterization of a Novel ATP-Dependent Caseinolytic Protease from the Marine BacteriumMicroorganisms · 2025Article
- Lysosomal activity in response to the incubation of pristine and functionalized carbon nanodots.iScience · 2025Article
- Platinum(IV) anticancer therapies and cathepsin B: innovative strategies for overcoming resistance in glioblastoma cells.Frontiers in cell and developmental biology · 2025Article
- BET-directed PROTACs in triple negative breast cancer cell lines MDA-MB-231 and MDA-MB-436.Breast cancer research and treatment · 2024Article
- Cytosolic serpins act in a cytoprotective feedback loop that limits ESX-1-dependent death ofmBio · 2024Article
- The Effects of Cathepsin B Inhibition in the Face of Diffuse Traumatic Brain Injury and Secondary Intracranial Pressure Elevation.Biomedicines · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Cathepsin B is a cysteine protease that normally functions within acidic lysosomes for protein degradation, but in numerous human diseases, cathepsin B translocates to the cytosol having neutral pH where the enzyme activates inflammation and cell death. Cathepsin B is active at both the neutral pH 7.2 of the cytosol and the acidic pH 4.6 within lysosomes. We evaluated the hypothesis that cathepsin B may possess pH-dependent cleavage preferences that can be utilized for design of a selective neutral pH inhibitor by (1) analysis of differential cathepsin B cleavage profiles at neutral pH compared to acidic pH using multiplex substrate profiling by mass spectrometry (MSP-MS), (2) design of pH-selective peptide-7-amino-4-methylcoumarin (AMC) substrates, and (3) design and validation of Z-Arg-Lys-acyloxymethyl ketone (AOMK) as a selective neutral pH inhibitor. Cathepsin B displayed preferences for cleaving peptides with Arg in the P2 position at pH 7.2 and Glu in the P2 position at pH 4.6, represented by its primary dipeptidyl carboxypeptidase and modest endopeptidase activity. These properties led to design of the substrate Z-Arg-Lys-AMC having neutral pH selectivity, and its modification with the AOMK warhead to result in the inhibitor Z-Arg-Lys-AOMK. This irreversible inhibitor displays nanomolar potency with 100-fold selectivity for inhibition of cathepsin B at pH 7.2 compared to pH 4.6, shows specificity for cathepsin B over other cysteine cathepsins, and is cell permeable and inhibits intracellular cathepsin B. These findings demonstrate that cathepsin B possesses pH-dependent cleavage properties that can lead to development of a potent, neutral pH inhibitor of this enzyme.
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.