ArticleBiochemistry2020
Rational Design of a Humanized Antibody Inhibitor of Cathepsin B.
Article in Biochemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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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
17 citing papers in PubMed, 21 citations in OpenAlex.
- Cathepsin Family Proteases in Prodrug Design: Recent Advances.ChemMedChem · 2026Review
- The evolving landscape of enzymatic technologies for precision synthesis of antibody-drug conjugates.Antibody therapeutics · 2026Review
- Synthesis of Bispecific Conjugates by ADP-Ribosyl Cyclases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Preclinical assessment of genetically modified exosomes for colorectal cancer immunotherapy.Journal of controlled release : official journal of the Controlled Release Society · 2026Article
- Downregulation of Cathepsin B expression alleviates periodontitis by reducing mitochondrial reactive oxygen species production and NOD-, LRR-, and pyrin domain-containing 3 -mediated pyroptosis.Frontiers in immunology · 2026Article
- New Therapeutic Options Against Clinically Relevant Proteases in Cancer Progression.Mini reviews in medicinal chemistry · 2026Review
- A versatile platform for chemical engineering of exosomes empowered by ADP-ribosyl cyclases.Nature communications · 2025Article
- Targeting prostate cancer with site-specific antibody-drug conjugates enabled by tandemly fused ADP-ribosyl cyclases.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Cathepsin B induces kidney diseases through different types of programmed cell death.Frontiers in immunology · 2025Review
- Synthesis of site-specific Fab-drug conjugates using ADP-ribosyl cyclases.Protein science : a publication of the Protein Society · 2024Article
- Rational design of humanized antibody inhibitors for cathepsin S.Archives of biochemistry and biophysics · 2024Article
- Substrate derived sequences act as subsite-blocking motifs in protease inhibitory antibodies.Protein science : a publication of the Protein Society · 2023Article
- Upconversion nanoparticle-based fluorescence resonance energy transfer sensing platform for the detection of cathepsin B activity in vitro and in vivo.Mikrochimica acta · 2023Article
- Cathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways.Cell death & disease · 2023Review
- Synthesis of Bispecific Antibody Conjugates Using Functionalized Poly-ADP-ribose Polymers.Biochemistry · 2023Article
- A two-trick pony: lysosomal protease cathepsin B possesses surprising ligase activity.RSC chemical biology · 2021Article
- A humanized antibody inhibitor for cathepsin L.Protein science : a publication of the Protein Society · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cathepsin B (CTSB) is an abundant cysteine protease that functions in both endolysosomal compartments and extracellular regions. A considerable number of preclinical and clinical studies indicate that CTSB is implicated in many human diseases. Expression levels and activity of CTSB significantly correlate with disease progression and severity. Current inhibitors of CTSB are lack of adequate specificity and pharmacological activities. Through structure-guided rational design, we hereby designed and generated a humanized antibody inhibitor targeting human CTSB. This was achieved by genetically fusing the propeptide of procathepsin B, a naturally occurring inhibitor of CTSB, into heavy chain complementarity-determining region 3 (CDR3H) of Herceptin that is used in the clinic for the treatment of breast cancer. The resulting antibody-propeptide fusion displayed high specificity for inhibiting CTSB proteolytic activity at nanomolar levels. Pharmacokinetic studies in mice revealed a plasma half-life of approximately 42 h for this anti-CTSB antibody inhibitor, comparable to that of the parental Herceptin scaffold. This study demonstrates a new approach for the efficient generation of humanized antibody inhibitors with high potency and specificity for human CTSB, which may be extended to develop antibody inhibitors against other disease relevant cathepsin proteases.
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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.