Use of fatty acid oxidation inhibitors as antimicrobials
Inventors
Philips, Jennifer A. • Moore, Kathryn • Chandra, Pallavi • Ouimet, Mireille
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
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.
Interested in licensing this patent?