ArticlePloS one2013
Improved BM212 MmpL3 inhibitor analogue shows efficacy in acute murine model of tuberculosis infection.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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
48 citing papers in PubMed.
- Gaining insights into MmpL3: combining structural and computational approaches to unlock transport and inhibitor-binding mechanisms.Acta crystallographica. Section D, Structural biology · 2026Article
- Scaffold Hopping in Tuberculosis Drug Discovery: Principles, Applications, and Case Studies.Journal of medicinal chemistry · 2025Review
- Article
- Applying green chemistry principles to iron catalysis: mild and selective domino synthesis of pyrroles from nitroarenes.Chemical science · 2023Article
- Revolutionizing control strategies against Mycobacterium tuberculosis infection through selected targeting of lipid metabolism.Cellular and molecular life sciences : CMLS · 2023Review
- Recent advances in mycobacterial membrane protein large 3 inhibitor drug design for mycobacterial infections.Expert opinion on drug discovery · 2023Review
- Molecular Mechanisms of MmpL3 Function and Inhibition.Microbial drug resistance (Larchmont, N.Y.) · 2023Review
- Structure and dynamics of the essential endogenous mycobacterial polyketide synthase Pks13.Nature structural & molecular biology · 2023Article
- Design, synthesis and evaluation of 1-(1,5-bis(4-substituted phenyl)-2-methyl-1RSC medicinal chemistry · 2023Article
- A Concise Synthesis of Pyrrole-Based Drug Candidates from α-Hydroxyketones, 3-Oxobutanenitrile, and Anilines.Molecules (Basel, Switzerland) · 2023Article
- Expanding the knowledge around antitubercular 5-(2-aminothiazol-4-yl)isoxazole-3-carboxamides: Hit-to-lead optimization and release of a novel antitubercular chemotype via scaffold derivatization.European journal of medicinal chemistry · 2023Article
- Microbiological profile, preclinical pharmacokinetics and efficacy of CRS0393, a novel antimycobacterial agent targeting MmpL3.Tuberculosis (Edinburgh, Scotland) · 2023Article
- The pathogenic mechanism of Mycobacterium tuberculosis: implication for new drug development.Molecular biomedicine · 2022Review
- Article
- Design, Synthesis, and Biological Evaluation of Pyrrole-2-carboxamide Derivatives as Mycobacterial Membrane Protein Large 3 Inhibitors for Treating Drug-Resistant Tuberculosis.Journal of medicinal chemistry · 2022Article
- Nano-Based Drug Delivery Systems of Potent MmpL3 Inhibitors for Tuberculosis Treatment.Pharmaceutics · 2022Article
- The Veterinary Anti-Parasitic Selamectin Is a Novel Inhibitor of theInternational journal of molecular sciences · 2022Article
- The multi-target aspect of an MmpL3 inhibitor: The BM212 series of compounds bind EthR2, a transcriptional regulator of ethionamide activation.Cell surface (Amsterdam, Netherlands) · 2021Article
- Cryo-EM structure and resistance landscape of M. tuberculosis MmpL3: An emergent therapeutic target.Structure (London, England : 1993) · 2021Article
- Structures of the mycobacterial membrane protein MmpL3 reveal its mechanism of lipid transport.PLoS biology · 2021Article
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
1,5-Diphenyl pyrroles were previously identified as a class of compounds endowed with high in vitro efficacy against M. tuberculosis. To improve the physical chemical properties and drug-like parameters of this class of compounds, a medicinal chemistry effort was undertaken. By selecting the optimal substitution patterns for the phenyl rings at N1 and C5 and by replacing the thiomorpholine moiety with a morpholine one, a new series of compounds was produced. The replacement of the sulfur with oxygen gave compounds with lower lipophilicity and improved in vitro microsomal stability. Moreover, since the parent compound of this family has been shown to target MmpL3, mycobacterial mutants resistant to two compounds have been isolated and characterized by sequencing the mmpL3 gene; all the mutants showed point mutations in this gene. The best compound identified to date was progressed to dose-response studies in an acute murine TB infection model. The resulting ED(99) of 49 mg/Kg is within the range of commonly employed tuberculosis drugs, demonstrating the potential of this chemical series. The in vitro and in vivo target validation evidence presented here adds further weight to MmpL3 as a druggable target of interest for anti-tubercular 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.