PulseExploreJournal ClubDebatesTrendingResearchersJournals
Instagram
HomeExploreJournal ClubTrending
Synapse
⌘+K
Synapse
May 9, 2026Journal of Medicinal Chemistry0 citations

Rhodanine-Inspired Development of Dual-Action Mycobacterium tuberculosis Protein Tyrosine Phosphatase B Inhibitors

View Full Paper
HSHaofan ShaoXWXiaoyu WuSCS I J I N G Cheng

Key Points

  • This research aims to develop effective inhibitors of MptpB, a protein in Mycobacterium tuberculosis, to combat tuberculosis.
  • Synthesis of rhodanine-inspired compounds targeting MptpB in Mycobacterium tuberculosis.
  • Evaluation of antituberculosis efficacy through MIC testing and comparisons with Rifampicin and Pretomanid.
  • Assessment of pharmacokinetic properties including metabolic stability and bioavailability in mice.
  • The lead compound showed a MIC of 1.94 μg/mL against Mycobacterium tuberculosis.
  • It exhibited a 345-fold selectivity over human PTP1B, indicating low toxicity to human cells.
  • In macrophage infection models, the compound outperformed existing treatments, reversing inhibition of the MAPK pathway.

Abstract

: 0.19 μM), good antituberculosis efficacy (MIC: 1.94 μg/mL), and high selectivity over human PTP1B (345-fold). It also demonstrated excellent metabolic stability, good permeability, acceptable bioavailability in mice, low cytotoxicity, and outperformed Rifampicin and Pretomanid in a macrophage infection model. Mechanistic studies showed that it reversed MptpB-mediated suppression of the macrophage MAPK pathway. This work validates the fusion strategy and identifies a promising lead targeting MptpB for further development.

Ask AI
Helpful
Bookmark
Share
View Full Paper

Cite This Study

Shao et al. (2026) studied this question.

synapsesocial.com/papers/69fecf16b9154b0b8287625dhttps://doi.org/10.1021/acs.jmedchem.6c00103
Ask AI
Helpful
Bookmark
Share
View Full Paper

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Identification of fusarielin M as a novel inhibitor of Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB)2020 · 31 citations
  2. 2Therapeutic Targeting of Protein Tyrosine Phosphatases from Mycobacterium tuberculosis2020 · 28 citations
  3. 3Discovery of biphenyls bearing thiobarbiturate fragment by structure-based strategy as Mycobacterium tuberculosis protein tyrosine phosphatase B inhibitors2022 · 7 citations
  4. 4A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis2000 · 1,042 citations
  5. 5Epalrestat: An Aldose Reductase Inhibitor for the Treatment of Diabetic Neuropathy2008 · 305 citations