{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["68(5)"],"submitter":["Sharma P"],"pubmed_abstract":["A dire need exists for novel drugs to treat <i>Mycobacterium tuberculosis</i> infection. In an effort to build on our early efforts targeting the MenG enzyme within the menaquinone biosynthetic pathway, we have pursued the optimization of diaryl amide JSF-2911 to address its poor metabolic stability and modest <i>in vitro</i> potency. A hit evolution campaign focused on modification of the amine substructure within this hit compound, resulting in a range of analogues that have been profiled extensively. Among these derivatives, JSF-4536 and JSF-4898 demonstrated significantly improved biological profiles, notably offering submicromolar MIC values versus <i>M. tuberculosis</i> and promising values characterizing the mouse liver microsome stability, aqueous solubility, and mouse pharmacokine"],"journal":["Journal of medicinal chemistry"],"pagination":["5774-5803"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12333353"],"repository":["biostudies-literature"],"pubmed_title":["Evolution of Small Molecule Inhibitors of &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt; Menaquinone Biosynthesis."],"pmcid":["PMC12333353"],"pubmed_authors":["Sukheja P","Cangialosi J","Johnson K","Sharma P","Ocke E","Jiang Q","Li SG","Zimmerman MD","Tsotetsi K","Kumar P","Park S","Russo R","Nelson AM","Penalva-Lopez S","Suryavanshi S","Morrison E","Singh P","Sharma V","Alland D","Thadkapally S","Sarathy JP","Freundlich JS"],"additional_accession":[]},"is_claimable":false,"name":"Evolution of Small Molecule Inhibitors of &lt;i&gt;Mycobacterium tuberculosis&lt;/i&gt; Menaquinone Biosynthesis.","description":"A dire need exists for novel drugs to treat <i>Mycobacterium tuberculosis</i> infection. In an effort to build on our early efforts targeting the MenG enzyme within the menaquinone biosynthetic pathway, we have pursued the optimization of diaryl amide JSF-2911 to address its poor metabolic stability and modest <i>in vitro</i> potency. A hit evolution campaign focused on modification of the amine substructure within this hit compound, resulting in a range of analogues that have been profiled extensively. Among these derivatives, JSF-4536 and JSF-4898 demonstrated significantly improved biological profiles, notably offering submicromolar MIC values versus <i>M. tuberculosis</i> and promising values characterizing the mouse liver microsome stability, aqueous solubility, and mouse pharmacokine","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Mar","modification":"2026-05-01T08:39:20.141Z","creation":"2026-04-19T03:07:59.362Z"},"accession":"S-EPMC12333353","cross_references":{"pubmed":["40035499"],"doi":["10.1021/acs.jmedchem.4c03156"]}}