By adding oxygen donors (like hydrogen peroxide) to metallorganic complexes (synthetic metalloporphyrins), we can mimic the action of CYP450 and generate milligram quantities of metabolites identical to those detected in biological samples. We can then test these metabolites for safety and drug-drug interaction potential to enable comprehensive safety evaluation or send them back to the client for in-house evaluation of pharmacological activity.
We Generate High-Milligram Quantities of Phase I Metabolites for:
Characterization of unique or abundant metabolites
in vitro characterization of drug-drug interaction
CYP inhibitor or inducer
P-gp substrate, inhibitor or inducer
We employ biomimetic oxidations to generate Phase I metabolites via non-enzymatic catalysis. Basically, it’s a protein-free, heme-like catalyst. In the presence of an oxygen donor such as H2O2, a reactive species is generated that can insert oxygen into a parent compound.
“Absorption Systems helped us solve a difficult problem with an innovative, quick, and cost-effective solution. Through the use of biomimetic oxidation, they were able to quickly produce enough of a target drug metabolite to help us figure out which of two isomers to synthesize “the old-fashioned way.”
– Bradley Wolfe, Ph.D., CMC Development Scientist II, SuperGen, Inc.
In another case, one of our lead scientists was named as co-inventor of international patent by our client in acknowledgment of our crucial contribution into synthesis and characterization of pharmacologically active metabolite.
Biomimetic oxidation methods offer several advantages
Preparative quantities of metabolites
No solubility limitations in most cases
Non-enzymatic catalysts are more rugged than enzymes
Can use higher concentrations of non-enzymatic catalysts
More versatile since it is not dependent on the activity of a particular CYP
More flexible in terms of reaction conditions, which enables a good correlation between metabolites generated biomimetically and enzymatically