ArticleNature medicine2014
Spectinamides: a new class of semisynthetic antituberculosis agents that overcome native drug efflux.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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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.
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Who cites it
88 citing papers in PubMed, 192 citations in OpenAlex.
- Naturally occurring dinactin targets cpsA protein and kills Mycobacterium tuberculosis by disrupting the proton motive force.Communications biology · 2026Article
- Sterilizing activity of spectinamide MBX-4888A when replacing linezolid in the Nix-TB regimen in the relapsing BALB/c mouse model of tuberculosis.Antimicrobial agents and chemotherapy · 2025Article
- Efflux pumps and membrane permeability contribute to intrinsic antibiotic resistance in Mycobacterium abscessus.PLoS pathogens · 2025Article
- Identification of a novel aminoglycoside nucleotidyltransferase gene in Morganella morganii from farm sewage.BMC microbiology · 2025Article
- Strategic re-engineering of antibiotics.Nature reviews bioengineering · 2025Article
- Revolutionizing tuberculosis treatment: Breakthroughs, challenges, and hope on the horizon.Acta pharmaceutica Sinica. B · 2025Review
- Recent advances in the biosynthetic pathway and structural modification of gentamicin.Frontiers in microbiology · 2025Review
- Development of tetracycline analogues with increased aqueous stability for the treatment of mycobacterial infections.Tuberculosis (Edinburgh, Scotland) · 2025Article
- Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Enhancing the therapeutic window for Spectinamide anti-tuberculosis Agents: Synthesis, Evaluation, and activation of phosphate prodrug 3408.Bioorganic & medicinal chemistry letters · 2024Article
- A modified BPaL regimen for tuberculosis treatment replaces linezolid with inhaled spectinamides.eLife · 2024Article
- Synthesis and antibacterial action of 3',6'-disubstituted spectinomycins.The Journal of antibiotics · 2024Article
- Investigation of the antimycobacterial activity of African medicinal plants combined with chemometric analysis to identify potential leads.Scientific reports · 2024Article
- Therapeutic developments for tuberculosis and nontuberculous mycobacterial lung disease.Nature reviews. Drug discovery · 2024Review
- Practical Considerations in Dose Extrapolation from Animals to Humans.Journal of aerosol medicine and pulmonary drug delivery · 2024Review
- The Antitubercular Activities of Natural Products with Fused-Nitrogen-Containing Heterocycles.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Development of 2nd generation aminomethyl spectinomycins that overcome native efflux inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- TargetingRSC medicinal chemistry · 2023Review
- Development of a Minimalistic Physiologically Based Pharmacokinetic (mPBPK) Model for the Preclinical Development of Spectinamide Antibiotics.Pharmaceutics · 2023Article
- ANT(9)-Ic, a Novel Chromosomally Encoded Aminoglycoside Nucleotidyltransferase from Brucella intermedia.Microbiology spectrum · 2023Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 6 institutions in 3 countries.
Funding
Abstract
Although the classical antibiotic spectinomycin is a potent bacterial protein synthesis inhibitor, poor antimycobacterial activity limits its clinical application for treating tuberculosis. Using structure-based design, we generated a new semisynthetic series of spectinomycin analogs with selective ribosomal inhibition and excellent narrow-spectrum antitubercular activity. In multiple murine infection models, these spectinamides were well tolerated, significantly reduced lung mycobacterial burden and increased survival. In vitro studies demonstrated a lack of cross resistance with existing tuberculosis therapeutics, activity against multidrug-resistant (MDR) and extensively drug-resistant tuberculosis and an excellent pharmacological profile. Key to their potent antitubercular properties was their structural modification to evade the Rv1258c efflux pump, which is upregulated in MDR strains and is implicated in macrophage-induced drug tolerance. The antitubercular efficacy of spectinamides demonstrates that synthetic modifications to classical antibiotics can overcome the challenge of intrinsic efflux pump-mediated resistance and expands opportunities for target-based tuberculosis drug discovery.
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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.