Applications

SiDMAP’s systems-biology approach to enabling drug development is based on the understanding that biological reactions to drugs are not isolated and that drug effect on a distant site (such as a protein kinase) will have impact on other functions. SiDMAP is able to capture the overall systemic-effect of the drugs in a sensitive, specific and quantitative manner. Our assays enable both pre-clinical and clinical drug development.

SiDMAP has broadly applied its assays to a vast array of human disease states including metabolic and cardiovascular disorders, cancer, or psychiatric/neurodegenerative conditions.

SiDMAP technology provides the tools necessary to measure drug effect on a disease process, in animals and humans. Our analysis of metabolic flux produces biomarkers of drug effect. Importantly, our sensitive approach analyzes drug effect rapidly (in hours or days). We measure the effects of drugs — modulation of kinetics of disease pathways in cells, live animals and patients. In this way, SiDMAP provides unique insights.

Using appropriate isotopes and study designs, the following pathways can be simultaneously measured (in vivo and in vitro):

Pathway Study

1. Glucose uptake (chemistry analysis of the culture media)

2. Direct glucose oxidation relative to glycolysis.

3. TCA cycle anaplerotic flux.

4. Direct glucose oxidation/non-oxidative ribose synthesis for RNA/DNA nucleotide syntheses.

5. Direct and indirect glycogen synthesis.

6. Cell cycle state (Cycle arrest, apoptosis, necrosis and their ratios)

7a. De novo fatty acid palmitate synthesis (13C enrichment in palmitate).

7b. Chain elongation into stearate and desaturation into oleate (13C enrichment in stearate and the isotope distribution ratios in palmitate, stearate and oleate).

7c. Long chain fatty acid (C:20, C:22, C24, C26) de novo synthesis (13C enrichment and distribution ratios in each species)

7d. Acetyl-CoA glucose carbon enrichment.

7e. De novo Cholesterol synthesis

8. De novo non-essential amino acid synthesis

9. Glucose oxidation in the pentose and TCA cycles.

10. Gluconeogenesis and futile cycling (ratios of appropriately chosen 13C label tracers) glucose and other recombined isotope labeled glucose species in the media.