ArticleChemMedChem2016
Substrate Fragmentation for the Design of M. tuberculosis CYP121 Inhibitors.
Article in ChemMedChem, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 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.
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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
8 citing papers in PubMed, 17 citations in OpenAlex.
- Structure-Function Analysis of the EssentialInternational journal of molecular sciences · 2024Article
- Synthesis, biological evaluation and computational studies of pyrazole derivatives asRSC medicinal chemistry · 2022Article
- A new strategy for hit generation: Novel in cellulo active inhibitors of CYP121A1 from Mycobacterium tuberculosis via a combined X-ray crystallographic and phenotypic screening approach (XP screen).European journal of medicinal chemistry · 2022Article
- Structure-Activity Relationship and Mode-Of-Action Studies Highlight 1-(4-Biphenylylmethyl)-1H-imidazole-Derived Small Molecules as Potent CYP121 Inhibitors.ChemMedChem · 2021Article
- Design and Synthesis of Imidazole and Triazole Pyrazoles asChemistryOpen · 2019Article
- Design and Synthesis of Bioisosteres of Acylhydrazones as Stable Inhibitors of the Aspartic Protease Endothiapepsin.ChemMedChem · 2018Article
- Cross-linking of dicyclotyrosine by the cytochrome P450 enzyme CYP121 fromThe Journal of biological chemistry · 2017Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The cyclo-dipeptide substrates of the essential M. tuberculosis (Mtb) enzyme CYP121 were deconstructed into their component fragments and screened against the enzyme. A number of hits were identified, one of which exhibited an unexpected inhibitor-like binding mode. The inhibitory pharmacophore was elucidated, and fragment binding affinity was rapidly improved by synthetic elaboration guided by the structures of CYP121 substrates. The resulting inhibitors have low micromolar affinity, good predicted physicochemical properties and selectivity for CYP121 over other Mtb P450s. Spectroscopic characterisation of the inhibitors' binding mode provides insight into the effect of weak nitrogen-donor ligands on the P450 heme, an improved understanding of factors governing CYP121-ligand recognition and speculation into the biological role of the enzyme for Mtb.
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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.