Use of fatty acid oxidation inhibitors as antimicrobials
Inventors
Philips, Jennifer A. • Moore, Kathryn • Chandra, Pallavi • Ouimet, Mireille
Assignees
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Publication Number
US-12616691-B2
Publication Date
2026-05-05
Expiration Date
Abstract
Methods of using small molecule inhibitors of fatty acid oxidation (FAO) as antimicrobials against intracellular Mycobacteria are disclosed. FAO inhibitors including etomoxir, trimetazidine, oxfenicine perhexeline and/or can be used alone, or in combination with known as antimycobacterial agents against intracellular Mycobacteria.
Core Innovation
Disclosed is a host-directed antimicrobial approach for treating Mycobacteria infection by administering trimetazidine to a subject. The method achieves a concentration ranging from about 1 nM to about 500 nM and reduces fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase.
Also disclosed is inhibiting intracellular growth of Mtb by administering trimetazidine at the same concentration range. The disclosure includes treating multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis contexts, with reduced fatty acid oxidation through inhibition of 3-ketoacyl-CoA thiolase.
Further disclosed is inhibiting intracellular growth of Mycobacterium abscessus by administering trimetazidine at a concentration ranging from about 1 nM to about 500 nM to reduce fatty acid oxidation. The disclosure additionally describes combination use with additional antimycobacterial agents and/or other host-modulating drugs.
Claims Coverage
The independent claims present three inventive features, each grounded on administering trimetazidine at about 1 nM to about 500 nM to reduce fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase.
Administering trimetazidine at 1 nM to 500 nM to treat Mycobacteria infection by inhibiting 3-ketoacyl-CoA thiolase
A method of treating a Mycobacteria infection in a subject in need thereof, comprising administering a dosage of trimetazidine to achieve a concentration ranging from about 1 nM to about 500 nM to reduce fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase.
Administering trimetazidine at 1 nM to 500 nM to inhibit intracellular growth of Mtb by inhibiting 3-ketoacyl-CoA thiolase
A method of inhibiting intracellular growth of Mtb in a subject in need thereof, comprising administering a dosage of trimetazidine to achieve a concentration ranging from about 1 nM to about 500 nM to reduce fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase.
Administering trimetazidine at 1 nM to 500 nM to inhibit intracellular growth of Mycobacterium abscessus by inhibiting 3-ketoacyl-CoA thiolase
A method of inhibiting intracellular growth of Mycobacterium abscessus in a subject in need thereof, comprising administering a dosage of trimetazidine to achieve a concentration ranging from about 1 nM to about 500 nM to reduce fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase.
The claimed inventive approach is to administer trimetazidine to achieve about 1 nM to about 500 nM, reducing fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase, with claim coverage directed to Mycobacteria infection, Mtb, and Mycobacterium abscessus.
Stated Advantages
Reduces fatty acid oxidation by inhibiting 3-ketoacyl-CoA thiolase.
Treats Mycobacteria infection in a subject in need thereof.
Inhibits intracellular growth of Mtb.
Inhibits intracellular growth of Mycobacterium abscessus.
Provides activity in multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis contexts.
Documented Applications
Treating a Mycobacteria infection in a subject in need thereof.
Inhibiting intracellular growth of Mtb in a subject in need thereof, including multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis contexts.
Inhibiting intracellular growth of Mycobacterium abscessus in a subject in need thereof.
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