ArticleAngewandte Chemie (International ed. in English)2022
Redesign of Rifamycin Antibiotics to Overcome ADP-Ribosylation-Mediated Resistance.
Article in Angewandte Chemie (International ed. in English), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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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
15 citing papers in PubMed, 20 citations in OpenAlex.
- Rifamycin Structural Modifications Attenuate PXR Binding and CYP3A4 Induction.Journal of medicinal chemistry · 2026Article
- Prodrug florfenicol amine is activated by intrinsic resistance to target Mycobacterium abscessus.Nature microbiology · 2025Article
- Next-generation rifamycins for the treatment of mycobacterial infections.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Toward a Bactericidal Oral Drug Combination for the Treatment ofACS infectious diseases · 2025Article
- Toward better cures forClinical microbiology reviews · 2024Review
- Rifabutin central nervous system concentrations in a rabbit model of tuberculous meningitis.Antimicrobial agents and chemotherapy · 2024Article
- Therapeutic developments for tuberculosis and nontuberculous mycobacterial lung disease.Nature reviews. Drug discovery · 2024Review
- Rifampicin has no role in treatment ofThe European respiratory journal · 2024Article
- Synthesis and in vitro Metabolic Stability of Sterically Shielded Antimycobacterial Phenylalanine Amides.ChemMedChem · 2024Article
- Exploring antibiotic resistance mechanisms inFrontiers in microbiology · 2024Review
- Innovative Phospholipid Carriers: A Viable Strategy to Counteract Antimicrobial Resistance.International journal of molecular sciences · 2023Review
- Blocking ADP-ribosylation expands the anti-mycobacterial spectrum of rifamycins.Microbiology spectrum · 2023Article
- ADP-ribosylation-resistant rifabutin analogs show improved bactericidal activity against drug-tolerantAntimicrobial agents and chemotherapy · 2023Article
- Synthesis and Characterization of Phenylalanine Amides Active againstJournal of medicinal chemistry · 2023Article
- Redesign of Rifamycin Antibiotics to Overcome ADP-Ribosylation-Mediated Resistance.Angewandte Chemie (International ed. in English) · 2022Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Rifamycin antibiotics are a valuable class of antimicrobials for treating infections by mycobacteria and other persistent bacteria owing to their potent bactericidal activity against replicating and non-replicating pathogens. However, the clinical utility of rifamycins against Mycobacterium abscessus is seriously compromised by a novel resistance mechanism, namely, rifamycin inactivation by ADP-ribosylation. Using a structure-based approach, we rationally redesign rifamycins through strategic modification of the ansa-chain to block ADP-ribosylation while preserving on-target activity. Validated by a combination of biochemical, structural, and microbiological studies, the most potent analogs overcome ADP-ribosylation, restored their intrinsic low nanomolar activity and demonstrated significant in vivo antibacterial efficacy. Further optimization by tuning drug disposition properties afforded a preclinical candidate with remarkable potency and an outstanding pharmacokinetic profile.
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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.