Application of Different Types of S9 in In Vitro Drug Metabolism Research
Key words: liver S9 fraction, hepatic S9 fraction, intestinal S9 fraction, lung S9 fraction, kidney S9 fraction, skin S9 fraction, human liver S9 fraction, monkey liver S9 fraction, beagle dog liver S9 fraction, rat liver S9 fraction, mouse liver S9 fraction, ADME, in vitro drug metabolism, liver S9 stability, S9 metabolic stability, subcellular fraction
1. IPHASE Products
Liver S9 Fraction
| Product Name | Specification |
|---|---|
| IPHASE Human Liver S9 Fraction, Mixed Gender | 0.5mL, 20mg/mL |
| IPHASE Monkey (Cynomolgus) Liver S9 Fraction, Male | 0.5mL, 20mg/mL |
| IPHASE Monkey (Rhesus) Liver S9 Fraction, Male | 0.5mL, 20mg/mL |
| IPHASE Dog (Beagle) Liver S9 Fraction, Male | 0.5mL, 20mg/mL |
| IPHASE Rat (Sprague-Dawley) Liver S9 Fraction, Male | 0.5mL, 20mg/mL |
| IPHASE Mouse (BALB/c) Liver S9 Fraction, Male | 0.5mL, 20mg/mL |
Intestinal S9 Fraction
| Product Name | Specification |
|---|---|
| IPHASE Human Intestinal S9 Fraction, Mixed Gender | 1mL, 4mg/mL |
| IPHASE Monkey (Cynomolgus) Intestinal S9 Fraction, Male, PMSF | 1mL, 4mg/mL |
Kidney, Lung, and Skin S9 Fractions
| Type | Product Name | Specification |
|---|---|---|
| Kidney | IPHASE Human Kidney S9 Fraction, Mixed Gender | 1mL, 5mg/mL |
| Lung | IPHASE Human Lung S9 Fraction, Mixed Gender | 1mL, 5mg/mL |
| Skin | IPHASE Dog (Beagle) Skin S9 Fraction, Male | 0.5mL, 4mg/mL |
2. In Vitro Drug Metabolism Stability Study
In vitro metabolic stability studies evaluate the biotransformation rate of compounds using biological matrices like liver microsomes, S9 fractions, and liver cells. These data support prediction of pharmacokinetics (PK) and ADME, enabling high-throughput screening and human clearance predictions. According to FDA, such studies should include recombinant human liver microsomes (HLM), hepatocytes, and cytochrome P450 enzymes.
3. Liver S9 Fraction
The liver S9 fraction (hepatic S9 fraction) is a mitochondria-free supernatant from liver parenchymal cell homogenate. It is rich in CYPs and other enzymes, useful for drug metabolism and drug-drug interaction studies. Applications include:
- Intrinsic clearance rate: An indicator of enzymatic activity; e.g., human liver S9 ~634.
- Metabolite identification: Characterizing drug metabolic pathways and active metabolites.
- Metabolic phenotype analysis: Assessing metabolic rates and drug interaction potential.
4. Intestinal S9 Fraction
Derived from intestinal tissue, this fraction contains enzymes like CYP3A4, UGT, and SULT. It is vital for studying first-pass metabolism, oral bioavailability, and gut-specific drug metabolism (e.g., SULT1B1).
5. Other Tissue Fractions
- Lung S9: Contains CYP1A1/2; used in assessing inhaled drug metabolism or environmental pollutants.
- Kidney S9: Contains UGT, SULT; used to evaluate renal drug clearance and nephrotoxicity.
- Skin S9: Useful for transdermal drug metabolism and activation of skin-specific enzymes (e.g., SULT1E1).
6. Species Differences in Liver S9 Fractions
Species-specific liver S9 fractions allow for comparison of metabolic rates and metabolite profiles. Typical species used include human, monkey, dog, rat, and mouse. Choosing appropriate models helps in predicting human response and improving translational research.
7. Conclusion
S9 fractions from various tissues provide indispensable tools for in vitro drug metabolism research. Liver S9 is especially valuable for intrinsic clearance, metabolite profiling, and interaction studies. Intestinal, lung, kidney, and skin S9 fractions offer complementary insights for tissue-specific drug evaluation. Cross-species S9 comparisons enhance preclinical model selection and data relevance.