Methods for drug discovery, disease treatment, and diagnosis using metabolomics
View Patent ↗The small molecule profiles of cells are compared to identify small molecules which are modulated in altered states. Cellular small molecule libraries, methods of identifying tissue sources, methods for treating genetic and non-genetic diseases, and methods for predicting the efficacy of drugs are also discussed.
1. A method for identifying small molecules affected by an agent comprising:
generating a small molecule profile of a cell treated with an agent, and
comparing said small molecule profile to a standard small molecule profile of a cell not treated with the agent; thereby identifying the small molecules affected by said agent in said cell, wherein said small molecule profile is obtained using one or more techniques which detect 50% or more of the small molecules in said cell.
2. The method of claim 1 , wherein said agent is a toxin.
3. The method of claim 1 , wherein said agent is a therapeutic agent.
4. The method of claim 3 , wherein said agent is a peptidomimetic, protein, peptide, nucleic acid, or small molecule.
5. The method of claim 1 , wherein said cell is obtained from a patient.
6. The method of claim 5 , wherein said patient is suffering from a metabolic, immunological, neurological, oncological, viral, or other disorder.
7. The method of claim 1 , wherein said small molecule profile is obtained from the mitochondria of the cell.
8. The method of claim 1 , wherein said small molecule profile is obtained from the nucleus of the cell.
9. The method of claim 1 , wherein said small molecule profiles are obtained using one or more of the following: HPLC, TLC, electrochemical analysis, mass spectroscopy, refractive index spectroscopy (RI), Ultra-Violet spectroscopy (UV), fluorescent analysis, radiochemical analysis, Near-InfraRed spectroscopy (Near-IR), Nuclear Magnetic Resonance spectroscopy (NMR), and Light Scattering analysis (LS).
10. A method for identifying small molecules affected by an agent, comprising:
generating a small molecule profile from a sample obtained from a subject treated with an agent, and
comparing said small molecule profile to a standard small molecule profile from a sample obtained from a subject not treated with an agent; thereby identifying the small molecules affected by said agent, wherein said small molecule profile is obtained using one or more techniques which detect 50% or more of the small molecules.
11. The method of claim 10 , wherein said agent is a therapeutic agent.
12. The method of claim 10 , wherein said agent is a peptidomimetic, protein, peptide, nucleic acid, or small molecule.
13. The method of claim 10 , wherein said agent is used for the treatment of a metabolic, immunological, neurological, oncological, viral, or other disorder.
14. The method of claim 10 , wherein at least one of the small molecules affected by said agent is indicative of efficacy of said agent.
15. The method of claim 10 , wherein said small molecule profile is compared to a standard small molecule profile using a subtraction profile.
16. The method of claim 10 , further comprising administering to a subject a second agent, wherein said second agent is used for the treatment of the same disorder as said agent, and obtaining a second small molecule profile.
17. The method of claim 16 , wherein said second small molecule profile is compared to said small molecule profile to identify compounds affected by said agent and said second agent.
18. The method of claim 10 , wherein said identified compounds comprise agent metabolites.
19. The method of claim 10 , wherein said identified compounds comprise endogenous cellular metabolites.
20. A method for identifying small molecules affected by a toxin, comprising:
generating a small molecule profile from a sample obtained from a subject treated with an toxin, and
comparing said small molecule profile to a standard small molecule profile from a sample obtained from a subject not treated with a toxin; thereby identifying the small molecules affected by said toxin, wherein said small molecule profile is obtained using one or more techniques which detect 50% or more of the small molecules.
21. The method of claim 20 , wherein said compounds comprise endogenous cellular metabolites.
22. The method of claim 20 , wherein said compounds comprises toxin metabolites.
23. A method of determining the toxicity of an agent, comprising:
generating a small molecule profile from a sample obtained from a subject treated with an agent; and
comparing said small molecule profile with a standard small molecule profile of one or more known toxins, thereby determining the toxicity of said agent, wherein said small molecule profile is obtained using one or more techniques which detect 50% or more of the small molecules.
24. The method of claim 23 , wherein said agent is a toxin.
25. The method of claim 23 , wherein said agent is a therapeutic agent.
26. The method of claim 23 , wherein said agent is a peptidomimetic, protein, peptide, nucleic acid, or small molecule.
27. The method of claim 2 , wherein said toxin is a bacterial toxin.
28. The method of claim 27 , wherein said bacterial toxin is an endotoxin or an exotoxin.
29. The method of claim 2 , wherein said toxin is cholera toxin, diphtheria toxin, verotoxin or enterotoxin.
30. The method of claim 4 , wherein said therapeutic agent is used for the treatment of a metabolic, immunological, neurological, oncological, viral, or other disorder.