ArticleNature communications2024
Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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
22 citing papers in PubMed.
- Targeting ClpP Protease: Emerging Therapeutic Strategies and Small-Molecule Modulators in Drug Discovery.Medicinal research reviews · 2026Review
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Proteostasis-targeted antibacterial strategies.Journal of microbiology (Seoul, Korea) · 2026Review
- ClpC1-targeting peptide natural products differentially dysregulate the proteome of Mycobacterium tuberculosis.Nature communications · 2026Article
- Drug resistance mechanisms inFrontiers in pharmacology · 2026Review
- Light-Activated Metal-Dependent Protein Degradation: A Heterobifunctional Ruthenium(II) Photosensitizer Targeting New Delhi Metallo-β-lactamase 1.Journal of the American Chemical Society · 2025Article
- Evolution of proteolysis-targeting chimeras (PROTAC) technology to overcome challenges of antimicrobial resistance.npj antimicrobials and resistance · 2025Review
- Synthesis of a Conformationally Fixed Bicyclomarin Derivative.ChemMedChem · 2025Article
- Allosteric control of the bacterial ClpC/ClpP protease and its hijacking by antibacterial peptides.The EMBO journal · 2025Article
- Systematic Determination of the Impact of Structural Edits on Peptide Accumulation into Mycobacteria.ACS chemical biology · 2025Article
- Total Synthesis of Mycoplanecin A.Organic letters · 2025Article
- CLIPPERs - Clip the right protein - a new tool for targeted proteolysis in bacteria.EMBO reports · 2025Article
- Targeted protein degradation in Escherichia coli using CLIPPERs.EMBO reports · 2025Article
- Chemical knockdown of Keap1 and homoPROTAC-ing allergic rhinitis.Acta pharmaceutica Sinica. B · 2025Article
- De novo designed protein guiding targeted protein degradation.Nature communications · 2025Article
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- PROteolysis TArgeting Chimeras (PROTACs) and beyond: targeted degradation as a new path to fight microbial pathogens.FEMS microbiology reviews · 2025Review
- Protein Degradation in Focus.Nature chemical biology · 2024Article
- PROTAC-ing tuberculosis.Nature chemical biology · 2024Article
- Navigating Antibacterial Frontiers: A Panoramic Exploration of Antibacterial Landscapes, Resistance Mechanisms, and Emerging Therapeutic Strategies.ACS infectious diseases · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antimicrobial resistance is a global health threat that requires the development of new treatment concepts. These should not only overcome existing resistance but be designed to slow down the emergence of new resistance mechanisms. Targeted protein degradation, whereby a drug redirects cellular proteolytic machinery towards degrading a specific target, is an emerging concept in drug discovery. We are extending this concept by developing proteolysis targeting chimeras active in bacteria (BacPROTACs) that bind to ClpC1, a component of the mycobacterial protein degradation machinery. The anti-Mycobacterium tuberculosis (Mtb) BacPROTACs are derived from cyclomarins which, when dimerized, generate compounds that recruit and degrade ClpC1. The resulting Homo-BacPROTACs reduce levels of endogenous ClpC1 in Mycobacterium smegmatis and display minimum inhibitory concentrations in the low micro- to nanomolar range in mycobacterial strains, including multiple drug-resistant Mtb isolates. The compounds also kill Mtb residing in macrophages. Thus, Homo-BacPROTACs that degrade ClpC1 represent a different strategy for targeting Mtb and overcoming drug resistance.
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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.