Use of fatty acid oxidation inhibitors as antimicrobials

Inventors

Philips, Jennifer A.Moore, KathrynChandra, PallaviOuimet, Mireille

Assignees

New York UniversityWashington University in St. Louis

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Publication Number

US-12616691-B2

Patent

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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