ArticlePloS one2020
Intracellular and in vivo evaluation of imidazo[2,1-b]thiazole-5-carboxamide anti-tuberculosis compounds.
Article in PloS one, 2020. 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
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
15 citing papers in PubMed.
- Safety, Tolerability, Pharmacokinetics, and Metabolism of Telacebec (Q203) for the Treatment of Tuberculosis: a Randomized, Placebo-Controlled, Multiple Ascending Dose Phase 1B Trial.Antimicrobial agents and chemotherapy · 2023Trial
- QcrB inhibitor Q203 (Telacebec) can synergize with clofazimine and clarithromycin to control a Mycobacterium avium infection.PloS one · 2026Article
- Recent progress in the synthetic and medicinal perspective of imidazo[2,1-Future medicinal chemistry · 2025Review
- Revolutionizing tuberculosis treatment: Breakthroughs, challenges, and hope on the horizon.Acta pharmaceutica Sinica. B · 2025Review
- Thiazole, Isatin and Phthalimide Derivatives TestedCurrent medicinal chemistry · 2024Review
- Target Identification in Anti-Tuberculosis Drug Discovery.International journal of molecular sciences · 2023Review
- Recent developments of imidazo[1,2-RSC medicinal chemistry · 2023Review
- Targeting the cytochrome bcMolecular diversity · 2022Review
- Design, synthesis and biological evaluation of benzo-[RSC advances · 2022Article
- Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents.Molecules (Basel, Switzerland) · 2022Review
- Prediction of QcrB Inhibition as a Measure of Antitubercular Activity with Machine Learning Protocols.ACS omega · 2022Article
- On drug discovery against infectious diseases and academic medicinal chemistry contributions.Beilstein journal of organic chemistry · 2022Article
- Chemical Classes Presenting Novel Antituberculosis Agents Currently in Different Phases of Drug Development: A 2010-2020 Review.Pharmaceuticals (Basel, Switzerland) · 2021Review
- SAR Analysis of Small Molecules Interfering with Energy-Metabolism inPharmaceuticals (Basel, Switzerland) · 2020Review
- Terminal Respiratory Oxidases: A Targetables Vulnerability of Mycobacterial Bioenergetics?Frontiers in cellular and infection microbiology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
Abstract
The imidazo[2,1-b]thiazole-5-carboxamides (ITAs) are a promising class of anti-tuberculosis agents shown to have potent activity in vitro and to target QcrB, a key component of the mycobacterial cytochrome bcc-aa3 super complex critical for the electron transport chain. Herein we report the intracellular macrophage potency of nine diverse ITA analogs with MIC values ranging from 0.0625-2.5 μM and mono-drug resistant potency ranging from 0.0017 to 7 μM. The in vitro ADME properties (protein binding, CaCo-2, human microsomal stability and CYP450 inhibition) were determined for an outstanding compound of the series, ND-11543. ND-11543 was tolerable at >500 mg/kg in mice and at a dose of 200 mg/kg displayed good drug exposure in mice with an AUC(0-24h) >11,700 ng·hr/mL and a >24 hr half-life. Consistent with the phenotype observed with other QcrB inhibitors, compound ND-11543 showed efficacy in a chronic murine TB infection model when dosed at 200 mg/kg for 4 weeks. The efficacy was not dependent upon exposure, as pre-treatment with a known CYP450-inhibitor did not substantially improve efficacy. The ITAs are an interesting scaffold for the development of new anti-TB drugs especially in combination therapy based on their favorable properties and novel mechanism of action.
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.