Bioenergetically active esters for health and disease
Compounds, compositions, and methods related to bioenergetic metabolism are provided. The compounds and com positions are suited to promote bioenergetic processes including cellular respiration and glycolytic flux and may be used to treat mitochondrial disorders, neurodegenerative diseases (such as Alzheimer's disease (AD), Parkinson's disease, and/or amyotrophic lateral sclerosis), multiple sclerosis, and/or epilepsy.
1. A compound of Formula I
or a pharmaceutically acceptable salt and/or solvate thereof,
wherein R 1 and R 2 are each independently
provided that at least one of R 1 and R 2 is not H.
2. The compound of claim 1 , wherein both R 1 and R 2 are
3. The compound of claim 1 , wherein the compound of Formula I is
or a pharmaceutically acceptable salt and/or solvate thereof;
or a pharmaceutically acceptable salt and/or solvate thereof;
or a pharmaceutically acceptable salt and/or solvate thereof;
or a pharmaceutically acceptable salt and/or solvate thereof;
or a pharmaceutically acceptable salt and/or solvate thereof; or
or a pharmaceutically acceptable salt and/or solvate thereof.
4. The compound of claim 1 , wherein the compound of Formula I is
a potassium salt of
a dipotassium salt of
a sodium salt of
a disodium salt of
a sodium potassium salt of
or a solvate thereof of any one of these.
5. A pharmaceutical composition comprising
the compound of claim 1 ; and
a pharmaceutically acceptable carrier.
6. A pharmaceutical composition comprising
an effective amount of the compound of claim 1 ; and
a pharmaceutically acceptable carrier;
wherein the effective amount of the compound is an amount of the compound effective to increase cellular respiration in a subject, increase glycolytic flux in a subject, treat a neurodegenerative disease in a subject, treat multiple sclerosis in a subject, treat epilepsy in a subject, treat a mitochondrial disorder in a subject, improve athletic performance in a subject, and/or improve cognitive performance in a subject.
7. The pharmaceutical composition of claim 6 , wherein the effective amount is one or both of an amount effective to treat Alzheimer's disease in a subject and an amount effective to treat Parkinson's disease in a subject.
8. A method for increasing cellular respiration in a cell, the method comprising contacting the cell with a compound of claim 1 .
9. A method of increasing a ratio of cytosolic NAD + to NADH in a cell, the method comprising contacting the cell with a compound of claim 1 .
10. A method of increasing glycolytic flux in a cell, the method comprising contacting the cell with a compound of claim 1 .
11. A method of increasing cellular respiration in a subject, the method comprising administering to the subject an effective amount of a compound of claim 1 .
12. The method of claim 11 , wherein the subject is suffering from a neurodegenerative disease, multiple sclerosis, and/or epilepsy.
13. A method of increasing glycolytic flux in a subject, the method comprising administering to the subject an effective amount of a compound of claim 1 .
14. The method of claim 13 , wherein the subject is suffering from a neurodegenerative disease, multiple sclerosis, and/or epilepsy.
15. A method of treating a subject suffering from a neurodegenerative disease, the method comprising administering an effective amount of a compound of claim 1 .
16. The method of claim 15 , wherein the neurodegenerative disease comprises one or more of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.
17. A method for increasing ketone levels in a subject, the method comprising administering to the subject a compound of claim 1 .
18. The method of claim 17 , wherein the method comprises administering to the subject an effective amount of the compound, wherein the effective amount is an amount that increases ketone levels in the subject.
19. A method of treating a subject suffering from multiple sclerosis, the method comprising administering an effective amount of a compound of claim 1 to the subject, wherein the effective amount is an amount effective to treat multiple sclerosis.
20. A method of treating a subject suffering from epilepsy, the method comprising administering an effective amount of a compound of claim 1 to the subject, wherein the effective amount is an amount effective to treat epilepsy.