ArticleJournal of medicinal chemistry2018
Fragment-Based Approach to Targeting Inosine-5'-monophosphate Dehydrogenase (IMPDH) from Mycobacterium tuberculosis.
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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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.
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.
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Who cites it
27 citing papers in PubMed, 61 citations in OpenAlex.
- Decoding GuaB: Machine Learning-Powered Discovery of Enzyme Inhibitors Against the SuperbugPharmaceuticals (Basel, Switzerland) · 2025Article
- Scaffold Hopping with Generative Reinforcement Learning.Journal of chemical information and modeling · 2025Article
- Role of the Mobile Active Site Flap in IMP Dehydrogenase Inhibitor Binding.ACS infectious diseases · 2025Article
- Differential effects of inosine monophosphate dehydrogenase (IMPDH/GuaB) inhibition inJournal of bacteriology · 2024Article
- Antibacterial activity of structurally diverse natural prenylated isobavachalcone derivatives.RSC advances · 2024Article
- Deciphering the allosteric regulation of mycobacterial inosine-5'-monophosphate dehydrogenase.Nature communications · 2024Article
- A journey into the regulatory secrets of theFrontiers in pharmacology · 2024Review
- Molecular dynamics articulated multilevel virtual screening protocol to discover novel dual PPAR α/γ agonists for anti-diabetic and metabolic applications.Molecular diversity · 2023Article
- Fragment-Based Lead Discovery Strategies in Antimicrobial Drug Discovery.Antibiotics (Basel, Switzerland) · 2023Review
- Using Graph-Based Signatures to Guide Rational Antibody Engineering.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Implications of Fragment-Based Drug Discovery in Tuberculosis and HIV.Pharmaceuticals (Basel, Switzerland) · 2022Review
- A d-Phenylalanine-Benzoxazole Derivative Reveals the Role of the Essential Enzyme Rv3603c in the Pantothenate Biosynthetic Pathway ofACS infectious diseases · 2022Article
- Antifungal metabolites, their novel sources, and targets to combat drug resistance.Frontiers in microbiology · 2022Review
- The Enzymatic Activity of Inosine 5'-Monophosphate Dehydrogenase May Not Be a Vulnerable Target forACS infectious diseases · 2021Article
- Prediction of rifampicin resistance beyond the RRDR using structure-based machine learning approaches.Scientific reports · 2020Article
- Molecule Property Analyses of Active Compounds forJournal of medicinal chemistry · 2020Review
- SyntaLinker: automatic fragment linking with deep conditional transformer neural networks.Chemical science · 2020Article
- Deep Generative Models for 3D Linker Design.Journal of chemical information and modeling · 2020Article
- Cryo-EM structures demonstrate human IMPDH2 filament assembly tunes allosteric regulation.eLife · 2020Article
- Combining structure and genomics to understand antimicrobial resistance.Computational and structural biotechnology journal · 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
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Tuberculosis (TB) remains a major cause of mortality worldwide, and improved treatments are needed to combat emergence of drug resistance. Inosine 5'-monophosphate dehydrogenase (IMPDH), a crucial enzyme required for de novo synthesis of guanine nucleotides, is an attractive TB drug target. Herein, we describe the identification of potent IMPDH inhibitors using fragment-based screening and structure-based design techniques. Screening of a fragment library for Mycobacterium thermoresistible ( Mth) IMPDH ΔCBS inhibitors identified a low affinity phenylimidazole derivative. X-ray crystallography of the Mth IMPDH ΔCBS-IMP-inhibitor complex revealed that two molecules of the fragment were bound in the NAD binding pocket of IMPDH. Linking the two molecules of the fragment afforded compounds with more than 1000-fold improvement in IMPDH affinity over the initial fragment hit.
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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.